BIOORGANIC & MEDICINAL CHEMISTRY
·
2021
·
IF 3.641
Zichen Xu,Bin Zhang,Zhixin Liao,Shaohua Gou
Hypoxia is one of the unique features of tumor physiology. Hypoxia inducible factor (HIF-1α), as a major transcription factor in response to hypoxia, has been considered as a promising tumor-specific target for anticancer therapy. The formation of a hypoxic microenvironment in tumors can decrease the curative effect of cytotoxic chemotherapeutic drugs. To promote the antitumor efficacy of chemotherapy by suppressing hypoxia, we designed and prepared a novel gemcitabine-based drug conjugate ( GEM -5 ) containing a HIF-1α inhibitor (YC-1). As expected, GEM -5 showed excellent antiproliferative activity (IC 50 = 0.03 μΜ under hypoxia) and remarkably induced the apoptosis of A2780 cells in vitro . Additionally, western blot analysis demonstrated that GEM -5 significantly down-regulated the expression of HIF-1α and up-regulated the expression of tumor suppressor p53. More importantly, GEM -5 effectively inhibited tumor growth in the A2780 xenograft mouse model and significantly ameliorated tumor hypoxia in vivo . This novel, simple, and effective strategy for overcoming tumor hypoxia and enhancing the antitumor effect of chemotherapeutic drugs has great potential in cancer therapy.
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CURRENT NEUROVASCULAR RESEARCH
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2022
·Vol. 19
·期 1
·61-72
·
IF 2.294
Xu Shu-Ying,Zeng Chun-Li,Ni Si-Ming,Peng Yong-Jun
Background: Acupuncture has been recommended as an alternative and complementary therapy for preventing and treating cerebral ischemia by the World Health Organization (WHO) for years. However, the mechanisms remain unclear. Accumulating evidence has shown that acupuncture can promote
angiogenesis to attenuate brain damage after ischemic stroke. In recent years, exosome- carried microRNAs (miRNAs) activated by acupuncture have proven effective in regulating pathological changes. We, therefore, investigated whether electro-acupuncture (EA) enhanced angiogenesis in cerebral
stroke via exosome-carried miR-210. Methods: We extracted and identified the exosomes from the serum of MCAO with EA treatment and injected them into MCAO rats for further observation. Simultaneously, miR-120 siRNA and HIF-1α inhibitor were transfected. Then, we evaluated the volume
of infarction, pathological changes, and expression levels of angiogenic related factors of each group of rats by TTC and HE staining, transmission electron microscope (TEM), western blot, and quantitative PCR (qPCR). Results: Compared with the MCAO group, EA-Exosome (EA-EXO) treatment
significantly decreased the infarct volume and the pathological damage, but miR-210 siRNA or HIF-1α inhibitor reversed the protective outcomes induced by EA-EXO. Moreover, EA-EXO treatment upregulated miR-210 and increased CD34, HIF-1α, VEGF, Notch1 protein, and mRNA expressions
compared to the MCAO group. MiR-210 siRNA or HIF-1α inhibitor treatments both down-regulated those angiogenic related proteins and mRNAs. Conclusion: EA treatment could activate the HIF-1α/VEGF/Notch 1 signal pathway to facilitate angiogenesis after ischemic stroke via exosomal
miR-210.
研究领域:
神经科学
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分子生物学
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中医药学
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中风研究
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Journal of Ginseng Research
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2022
·
IF 5.735
Hong-Yan Guo,Yue Xing,Yu-Qiao Sun,Can Liu,Qian Xu,Fan-Fan Shang,Run-Hui Zhang,Xue-Jun Jin,Fener Chen,Jung Joon Lee,Dongzhou Kang,Qing-Kun Shen,Zhe-Shan Quan
Background Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20( R )-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20( R )-panaxotriol and investigate its antitumor activity in vivo and in vitro . Methods Here, 20( R )-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by 1 H-NMR, 13 C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2 H -pyran-2-yl)hexadecahydro-1 H -cyclopenta[a]phenanthren-3-yl( tert -butoxycarbonyl)glycinate ( A11 ). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC 50 < 0.3 μM) was more than 100 times higher than that of 20( R )- panaxotriol (IC 50 > 30 μM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20( R )-panaxotriol ( p < 0.01) in vivo . Conclusion To our knowledge, this is the first study to report the production of derivative A11 from 20( R )-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.
研究领域:
药理学
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肿瘤学
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有机化学
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生物化学
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Acta Biomaterialia
·
2026
·
IF 10.4
Jiakun Guo,Jintao Huang,Yan Wang,Juan Sun,Shang Liu,Chao Deng,Jian Lu,Zhiyuan Zhong
Transarterial chemoembolization (TACE) is a primary treatment option for unresectable hepatocellular carcinoma (HCC). Its clinical efficacy is, however, challenged by hypoxic and immunosuppressive tumor microenvironment. Herein, we report that absorbable microspheres (Asphere) with sustained co-delivery of hypoxia-inducible factor 1 (HIF-1) inhibitor, acriflavine (ACF), effectively reverse tumor hypoxia and boost TACE therapy of advanced HCC. Interestingly, Asphere demonstrates nearly quantitative loading of both epirubicin (EPI) and ACF within 1 min, while achieving sustained release of the dual drugs over 8 weeks. EPI/ACF-loaded Aspheres (EA@Asphere) greatly inhibit hypoxia-associated proteins and augment immunogenic cell death in HCC cells under hypoxic conditions, which in turn triggers maturation of dendritic cells (DCs) and secretion of pro-inflammatory cytokines. In H22 murine hepatoma model, EA@Asphere markedly boosts DC maturation, CD8 + T cell infiltration, and macrophage polarization from M2 to M1, achieving complete tumor regression in 2 out of 7 mice. EA@Asphere further blocks tumor vasculature in orthotopic VX2 liver tumor in rabbits, alleviates hypoxia, and suppresses tumor progression and metastasis. Thus, Asphere co-delivering HIF-1 inhibitors holds significant translational potential to boost TACE therapy in advanced HCC. Statement of significance This work introduces an approach to enhance transarterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC) by co-delivering HIF-1 inhibitor acriflavine (ACF) and epirubicin (EPI) via absorbable microspheres (Asphere). Asphere demonstrates swift dual drug loading, sustained 8-week release, and simultaneous reversal of hypoxia and immunosuppression, addressing critical challenges of current TACE therapy. In preclinical studies, EA@Asphere significantly suppresses hypoxia-associated protein expression, enhances immunogenic cell death, promotes dendritic cell maturation, and reprograms tumor microenvironment, achieving significant inhibition of the tumor progression and metastasis. These findings offer transformative potential to improve clinical outcomes in advanced HCC, holding broad interest for researchers and clinicians in oncology and drug delivery.
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Chinese Medicine
·
2026
·Vol. 21
·期 1
·146
·
IF 7.4
Yang Junfa,Shu Min,Fang Hui,Yang Fan,Li Jiahe,Sun Yuansong,Li He,Xu Tao
Background Liver fibrosis is a representative scarring response that can ultimately lead to liver cancer. However, relevant antifibrotic drugs for the effective treatment of liver fibrosis in humans have not yet been identified. 6-Shogaol is derived from natural products and exhibits multiple biological activities, including anti-inflammatory and antioxidant properties; however, its efficacy and potential mechanism of action against liver fibrosis remains unclear. This study aimed to examine the anti-fibrotic properties and potential mechanisms of action of 6-Shogaol. Methods Two liver fibrosis mouse models (carbon tetrachloride (CCl 4 ) and bile duct ligation (BDL)) were constructed to evaluate the anti-fibrotic properties of 6-Shogaol in vivo . Transforming growth factor-β1 (TGF-β1)-induced human hepatic stellate cells (HSCs) LX-2 cells were used as in vitro models. Network pharmacology analysis was introduced to explore the key targets of 6-Shogaol regarding the mechanisms on liver fibrosis. Molecular docking, molecular dynamics simulations, drug affinity reactivity target stability (DARTS) and isothermal titration calorimetry (ITC) were used to detect the affinity and binding between 6-Shogaol and its target. Additionally, we invested the mechanism of 6-Shogaol through RNA sequencing combined with Western blotting, oxygen consumption rate (OCR), extracellular acidification rate (ECAR), immunofluorescence co-localization, histopathology, immunohistochemical staining and RT-qPCR. Results The results showed that 6-Shogaol remarkably alleviated CCl 4 - and BDL-induced liver fibrosis in mice, including observations of improved liver function, decreased activity of HSCs, and decreased extracellular matrix (ECM) deposition. In an in vitro model, 6-Shogaol suppressed TGF-β1-induced LX-2 activation. Mechanistically, RNA sequence analysis revealed that the effect of 6-Shogaol on liver fibrosis is linked to glycolytic reprogramming. 6-Shogaol suppressed HSCs glycolysis by decreasing glycolytic enzymes (HK2, PKM2, and GLUT1) and glycolytic metabolite levels (lactic acid and pyruvic acid). Furthermore, network pharmacology suggested HIF-1α as a potential 6-Shogaol target. Molecular docking, molecular dynamics simulations, DARTS, and ITC confirmed that 6-Shogaol could directly bind to HIF-1α. Interestingly, we demonstrated that HIF-1α knockout significantly inhibited HSCs glycolysis and activation, whereas the overexpression of HIF-1α increased HSCs glycolysis and activation. Moreover, specific knockout of HIF-1α did not enhance the suppressive effect of 6-Shogaol on HSCs activation or fibrosis-associated protein expression in vivo . Conclusion These findings showed that 6-Shogaol ameliorated liver fibrosis by modulating the expression of HIF-1α associated with glycolysis reprogramming and validate 6-Shogaol as a promising therapeutic strategy for liver fibrosis. Graphical
The alternative text for this image may have been generated using AI.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
·Vol. 24
·期 1
·391
·
IF 15
Chen Ying,Peng De-Wei,Jiang Sheng-Rui,Shao Qian-Chun,Zhang Yi-Cong,Chi Zai-Long
Objective Retinal neovascularization is a leading cause of irreversible blindness worldwide. Chinese herbal medicines have unique therapeutic properties, such as antioxidant, anti-inflammatory, and neuroprotective effects. This study aims to investigate the therapeutic effects and underlying mechanisms of the Chinese medicinal herb Curcuma longa -derived extracellular vesicle-like particles (CL-EVLPs) in a mouse model of retinal neovascularization. Methods CL-EVLPs were extracted from fresh Curcuma longa rhizomes through differential centrifugation and sucrose density gradient centrifugation and characterized by transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA), and western blot analysis of EVLP-associated protein markers. CL-EVLPs were administered to oxygen-induced retinopathy (OIR) model mice via intravitreal injection. The therapeutic effects were evaluated using retinal flat mounts, fundus fluorescein angiography (FFA), and reactive oxygen species (ROS) staining. The underlying molecular mechanisms were explored through metabolomics, transcriptomics, and network pharmacology analyses, and the expression levels of relevant factors were quantified using real-time polymerase chain reaction (PCR) or western blotting. In vitro experiments were conducted using human retinal microvascular endothelial cells (hRMECs) and BV2 microglia. Results CL-EVLPs exhibited typical EV-like characteristics, including a saucer‑ or cup‑shaped morphology, a mean diameter of 140.7 nm, and enrichment of the EV‑related protein ARF1. CL-EVLPs effectively inhibited neovascularization in the OIR model, as evidenced by reduced pathological neovascular tufts and avascular zones and decreased vascular permeability and tortuosity. Furthermore, CL-EVLPs significantly decreased ROS production in the retinas of OIR mice. Mechanistically, CL-EVLPs inhibited HIF-1α/VEGF/ERK signaling and activated the NRF2/HO-1 antioxidant pathway. In vitro experiments confirmed that CL-EVLPs inhibited endothelial cell viability and alleviated oxidative stress in microglia. Integrated network pharmacology and metabolomics analyses proved that the cargo molecules of CL-EVLPs, such as curcumin and its derivatives, auraptene, and triptophenolide, exhibit regulatory antioxidant and anti-inflammatory effects and modulate multiple signaling pathways associated with retinal neovascular diseases. Conclusion CL-EVLPs effectively suppress retinal neovascularization by inhibiting the HIF-1α/VEGFA/ERK axis and activating the NRF2/HO-1 pathway. This study suggests that CL-EVLPs, as a multitarget therapeutic strategy, hold promising clinical translational potential for the treatment of retinal neovascular diseases. Graphical abstract The alternative text for this image may have been generated using AI.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
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2026
·Vol. 53
·期 9
·e70153
·
IF 2.5
Renchuang Cao,Qingying Meng,Gengyuan Li,Shumei Yuan,Chunmei Li,Xin Zhao,Dongmei Zhang
Heat shock factor 2 (HSF2) and hypoxia‐inducible factor 1α are activated by angiotensin II (ANGII) in cardiomyocytes. The endoplasmic reticulum (ER) stress plays a critical role in cardiac hypertrophy. Moreover, HIF‐1α is known to be regulated by HSF2 in tumour cells. In this study, we hypothesised and clarified whether HSF2 trans‐activated HIF‐1α through initiation of ER stress in hypertrophic cardiomyocytes. Myocardial hypertrophy was induced by the treatment of ANGII. Expression of the gene or protein was assessed by applying RT‐PCR, WB, ICC and IHC. Luciferase and CHIP were applied to detect the transcription of HIF‐1α by HSF2. Both in vitro and in vivo, the expression of HIF‐1α, ER stress markers and HSF2 was increased in ANGII‐treated hypertrophic cardiomyocytes. Blocking ER stress suppressed the expression of HSF2 and HIF‐1α in ANGII‐treated cardiomyocytes. Silencing HSF2 inhibited HIF‐1α, thereby reducing hypertrophy but had no effect on ER stress. Similarly, silencing HIF‐1α reduced hypertrophy without affecting ER stress or HSF2 expression. HSF2 transcriptionally activated HIF‐1α. We concluded that ER stress induced by ANGII activates HSF2, which then trans‐activates HIF‐1α, promoting cardiac hypertrophy.
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Acta Biomaterialia
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2025
·
IF 9.6
Yushen Wang,Xinyu Li,Junlei Han,Feng Kong,Zhipeng Xu,Huili Hu,Li Wang
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disease characterized by lipid zonation, which is closely linked to the functional zonation of liver lobules. However, existing models cannot faithfully replicate the oxygen gradient that regulates liver zonation, hindering a clear understanding of the progression and intervention mechanisms in MASLD. Here, we constructed a MASLD liver-zonation-on-a-chip that utilizes an engineering strategy based on “environmental oxygen convection and diffusion”, achieving a controllable oxygen concentration gradient (3.7%-8.9%) that closely mimics the in vivo hepatic microenvironment. This platform successfully recapitulates the typical features and clinicopathological phenotypes of the liver lobule while enabling continuous monitoring of liver injury. We found that upregulation of the oxygen-sensing factor HIF-2α does not directly promote lipid accumulation. Instead, it indirectly facilitates the progression of MASLD by enhancing the transcriptional activity of β-catenin through the WNT signaling pathway (e.g., AXIN2, DVL1 ). As regulators of the damage process, HIF-2α and β-catenin may be targeted to improve outcomes in MASLD. Significance of statement Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common liver disorder characterized by lipid zonation, which is closely related to the functional zonation of liver lobules. However, existing models are unable to accurately replicate the oxygen (O 2 ) gradients that regulate liver zonation, a limitation that hinders their ability to accurately reflect hepatocyte pathophysiology and obstructs understanding of the mechanisms underlying MASLD progression. This study constructs a liver-zonation-on-a-chip with a controllable physiological O₂ gradient and integrated biosensing for non-destructive injury monitoring. The O 2 gradient chip successfully replicates liver lobule zonation, providing an engineering approach to overcoming the challenge of low regional heterogeneity in liver organoids. The application of the liver-zonation-on-a-chip in pathological assessments has also been thoroughly evaluated, offering potential solutions for MASLD interventions.
研究领域:
生物医学工程
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肝病学
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微生理系统
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分子生物学
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代谢性疾病
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Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-13
·
IF 5.116
Chai Miaomiao,Gu Ce,Shen Qihua,Liu Jiaxing,Zhou Yi,Jin Ziyang,Xiong Wanli,Zhou Yan,Tan Wensong
Background and aim Inadequate vascularization is a challenge in bone tissue engineering because internal cells are prone to necrosis due to a lack of nutrient supply. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to construct prevascularized bone tissue in osteogenic induction medium (OIM) in vitro. The angiogenic capacity of HUVECs was limited in the coculture system. In this study, the effects of the components in the medium on HUVEC angiogenesis were analyzed. Methods The coculture system was established in OIM. Alizarin red staining and alkaline phosphatase staining were used to assess the osteogenic ability of MSCs. A Matrigel tube assay was used to assess the angiogenic ability of HUVECs in vitro. The proliferation of HUVECs was evaluated by cell counting and CCK-8 assays, and migration was evaluated by the streaked plate assay. The expression levels of angiogenesis-associated genes and proteins in HUVECs were measured by qRT-PCR and Western blotting, respectively. Results Dexamethasone in the OIM suppressed the proliferation and migration of HUVECs, inhibiting the formation of capillary-like structures. Our research showed that dexamethasone stimulated HUVECs to secrete tissue inhibitor of metalloproteinase (TIMP-3), which competed with vascular endothelial growth factor (VEGF-A) to bind to vascular endothelial growth factor receptor 2 (VEGFR2, KDR). This effect was related to inhibiting the phosphorylation of ERK and AKT, which are two downstream targets of KDR. However, under hypoxia, the enhanced expression of hypoxia-inducible factor-1α (HIF-1α) decreased the expression of TIMP-3 and promoted the phosphorylation of KDR, improving HUVEC angiogenesis in the coculture system. Conclusion Coculture of hypoxia-preconditioned HUVECs and MSCs showed robust angiogenesis and osteogenesis in OIM, which has important implications for prevascularization in bone tissue engineering in the future.
研究领域:
组织工程
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细胞生物学
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分子生物学
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生物医学工程
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2021
·
IF 6.514
Fan-Fan Shang,Jing Ying Wang,Qian Xu,Hao Deng,Hong-Yan Guo,Xuejun Jin,Xiaoting Li,Qing-Kun Shen,Zhe-Shan Quan
Four series of hypoxia-inducible factor-1 alpha (HIF-1α) functioning derivatives stemming from modifications to the C-29 carboxyl group of celastrol were designed and synthesized, and their anticancer activities were evaluated. To address the structure and activity relationship of each derivative, extensive structural changes were made. HRE luciferase reporter assay demonstrated that 12 modified compounds showed superior HIF-1α inhibitory activity. Among them, compound C6 exhibited the best features: firstly, the strongest HIF-1α inhibitory activity (IC 50 = 0.05 μM, 5-fold higher than that of celastrol); secondly, lower cytotoxicity (22-fold lower, C6-16.85 μM vs celastrol-0.76 μM). Thus, the safety factor of C6 was about 112 times higher than that of celastrol. Western blot assay indicated that C6 may inhibit the expression of HIF-1α protein in cells. Additionally, C6 hindered tumor cell cloning , migration and induced cell apoptosis . It is worth mentioning that in the mouse tumor xenograft model, C6 (10 mg/kg) displayed good antitumor activity in vivo , showing a better inhibition rate (74.03%) than the reference compound 5-fluorouracil (inhibition rate, 59.58%). However, the celastrol treatment group experienced collective death after four doses of the drug. Moreover, C6 minimally affected the mouse weight, indicating that its application in vivo has little toxic effect. H&E staining experiments show that it could also exacerbate the degree of tumor cell damage. The results of water solubility experiment show that the solubility of C6 is increased by 1.36 times than that of celastrol. In conclusion, C6 is a promising antitumor agent through HIF-1α pathway.
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EXPERIMENTAL CELL RESEARCH
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2023
·
IF 3.7
Mingmei Li,Li Li,Xiaoxiao Cheng,Longyu Li,Kaijia Tu
Background Ovarian cancer has been a worldwide health burden for women and its progression is highly hypoxia-independent. Here, we investigated the exact mechanisms by which hypoxia contributes to the malignant progression of ovarian cancer. Method MTT, transwell, colony formation, and scratch wound healing assays were carried out for cellular functions. The underlying mechanism by which hypoxia functions was explored by RNA-seq, enrichment analysis, western blotting, qRT-PCR, flow cytometry, ChIP, luciferase reporter, and ELISA. Finally, animal experiments including the xenograft model and tumor metastasis model were constructed to validate the role of SLC2A12 in vivo . Results Hypoxia treatment promoted the cell proliferation, mobility, and colony growth abilities of the two ovarian cancer cell lines HO-8910 and A2780. RNA-seq and enrichment analysis showed that SLC2A12 was hyper-expressed under hypoxia condition and it may be related to glutathione and lipid metabolism. Besides, the expression of SLC2A12 was negatively correlated with overall survival. Hypoxia suppressed ferroptosis by SLC2A12 because silencing SLC2A12 declined the cell viability of HO-8910 and A2780 cells under hypoxia conditions, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) breached that result and upregulated the expression of glutathione peroxidase 4 (GPX4). Moreover, hypoxia increased the expression of hypoxia inducible factor 1 A (HIF-1A), and the accumulated HIF-1A binds to hypoxia inducible factor 1 B (HIF1B) to form HIF-1 complex, then promoted the binding of hypoxic response elements (HRE) to SLC2A12 promoter by HIF-1/HRE signal. Subsequently, SLC2A12 regulated glutathione metabolism and in turn inhibited ferroptosis. The animal experiments indicated that silencing SLC2A12 could significantly inhibit tumor growth and metastasis in vivo . Conclusion Hypoxia promoted ovarian cancer progression by upregulating SLC2A12 and then regulating glutathione metabolism to inhibit ferroptosis.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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International Journal of Ophthalmology
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2019
·
IF 1.189
Li-Fei Wang,Zhong-Yang Yan,Ya-Lin Li,Yan-Hui Wang,Sheng-Juan Zhang,Xin Jia,Lu Lu,Yan-Xia Shang,Xin Wang,Yun-Huan Li,Shan-Yu Li
AIM To explore the effect of Obtusifolin on retinal pigment epithelial cell growth under hypoxia. METHODS In vitro chemical hypoxia model of ARPE-19 cells was established using cobalt chloride (CoCl 2 ). Cell viability was tested by cell counting kit-8 (CCK-8) assay. Western blot and real-time quantitative polymerase chain reaction were applied to detect proteins and mRNAs respectively. Flow cytometry was used to examine the cell cycle. Secretion of vascular endothelial growth factor (VEGF) was tested by using enzyme linked immunosorbent assay (ELISA). RESULTS Under the chemical hypoxia model established by CoCl 2 , hypoxia inducible factor-1α (HIF-1α) mRNA and protein levels was up-regulated. Cell viability was increased and the proportion of S phase was higher. Obtusifolin could reduce cell viability under hypoxic conditions and arrest cells in G1 phase. Obtusifolin reduced the expression of Cyclin D1 and proliferating cell nuclear antigen (PCNA) in the hypoxic environment and increased the expression of p53 and p21. The levels of VEGF, VEGFR2 and eNOS proteins and mRNA were significantly increased under hypoxia while Obtusifolin inhibited the increasing. CONCLUSION Obtusifolin can inhibit cell growth under hypoxic conditions and down-regulate HIF-1/VEGF/eNOS secretions in ARPE-19 cells.
研究领域:
眼科学
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细胞生物学
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分子生物学
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