Cancer Management and Research
·
2019
·
IF 2.243
Lehe Yang,Jifa Li,Lingyuan Xu,Shichong Lin,Youqun Xiang,Xuanxuan Dai,Guang Liang,Xiaoying Huang,Jiandong Zhu,Chengguang Zhao
Background Non-small-cell lung cancer (NSCLC) comprises about 85% of all lung cancers and is usually diagnosed at an advanced stage with poor prognosis. The IL-6/STAT3 signaling pathway plays a pivotal role in NSCLC biology. Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that Rhein has significant antitumor effects, supporting the potential uses of Rhein as an antitumor agent.Methods Cell viability and colony formation were performed to examine Rhein’s potent anti-proliferative effect in human NSCLC cell lines PC-9, H460 and A549. Flow cytometry-based assay was employed to study whether Rhein could affect cell apoptosis and cycle. The expression level of P-STAT3, apoptosis and cycle-related proteins Bcl-2, Bax, MDM2, CDC2, P53 and CyclinB1 were detected by Western blotting. The xenograft models were used to evaluate the in vivo effect of Rhein.Results We found that Rhein could significantly reduce the viability and stimulate apoptosis in human NSCLC cells in a dose-dependent manner. Western blot analysis results suggested that the antitumor effect of Rhein might be mediated via STAT3 inhibition. Rhein upregulated the expression of the proapoptotic protein Bax and downregulated the expression of the antiapoptotic protein Bcl-2. In addition, Rhein induced the arrest of NSCLC cells in the G2/M phase of the cell cycle and dose dependently inhibited the expression of cycle-related proteins. The Rhein also inhibited tumor growth in H460 xenograft models.Conclusion Rhein shows potent efficacy against NSCLC through inhibiting the STAT3 pathway. Our results also suggest that Rhein has a promising potential to be used as a novel antitumor agent for the treatment of NSCLC.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Shuzhen Mao,Jiahui Huang,Junyan Li,Fang Sun,Qilian Zhang,Qing Cheng,Wei Zeng,Dongya Lei,Shiyan Wang,Jing Yao
Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by mucosal damage and impaired epithelial barrier function. While glycyl-l-histidyl-l-lysine-copper (GHK-Cu) exhibits known anti-inflammatory properties, its therapeutic mechanisms in UC remain undefined. This study was designed to systematically evaluate the therapeutic potential of GHK-Cu in a dextran sulfate sodium (DSS)-induced murine model of UC, with particular emphasis on elucidating its regulatory effects on the NAD-dependent deacetylase sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods: UC was induced in BALB/c mice with 3% DSS for 14 days. The protein expression levels of tight junction associated protein-1 (ZO-1), Occludin, inflammatory factors interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, SIRT1, STAT3, p-STAT3, and retinoic acid receptor-related orphan receptor gamma t (RORγt) were detected by Western blot. Histopathological changes were evaluated by Hematoxylin and Eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS). Network pharmacology and molecular docking were used to predict the core targets of GHK Cu in the treatment of UC. An in vitro UC model was also established in mouse peritoneal macrophages (MPMs) using lipopolysaccharide (LPS), and a co culture model was constructed using mouse colonic epithelial cells (MCECs) and MPMs to examine the role of GHK Cu in promoting mucosal healing. STAT3 was silenced by gene transfection technology to verify the core role of STAT3 in GHK Cu treatment of UC.Results: GHK-Cu alleviated weight loss, improved the disease activity index (DAI), reduced colonic edema and shortening, attenuated inflammatory damage, increased goblet cell numbers, suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and promoted mucosal repair. Additionally, a co-culture system of MCECs and MPMs revealed that GHK-Cu facilitated MCECs healing, impaired by DSS, by upregulating ZO-1 and Occludin expression. Subsequently, network pharmacology and molecular docking identified SIRT1 as a potential target of GHK-Cu. Results showed that GHK-Cu upregulated SIRT1 protein expression and suppressed the expression of phosphorylated p-STAT3 in colon tissue and MCECs of the co-culture model. Our findings revealed that after transfection with STAT3-targeting siRNA (siSTAT3), the stimulant effect of GHK-Cu on the healing of MCECs and the effect on the protein expression of ZO-1 and Occludin is canceled. Nevertheless, after transfection with siSTAT3, it could inhibit the expression of inflammatory factors in conjunction with GHK-Cu. Furthermore, we found that GHK-Cu could inhibit RORγt expression in the colon tissue of UC mice.Discussion: This study found that GHK-Cu demonstrated significant therapeutic effects in DSS-induced UC in mice. GHK-Cu may promote mucosal healing and enhance tight junction protein expression by regulating the SIRT1/STAT3 pathway. In addition to suppressing p-STAT3 expression, GHK-Cu may utilize additional pathways to inhibit inflammatory factors. Furthermore, GHK-Cu may reduce the number of Th17 cells. In summary, GHK-Cu may treat UC by acting on the SIRT1/STAT3 pathway.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-9
·
IF 6.1
Zheng Rongji,Guan Tian,Hong Chaoqun,Yao Yao,Fang Yutong,Huang Wei,Chen Chunfa,Zeng Huancheng,Huang Jiman,Lin Hui,Chen Bingfeng,Zhang Rendong,Chen Dongmei,Ding Zhechun,Zeng Haoyu,Wu Jundong
ObjectivesSTAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs).Methods PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs.Results C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway.Conclusion sIn this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.
研究领域:
肿瘤学
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分子生物学
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转化医学
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DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 46
·26371-26376
·
IF 2.936
Qiu Li,Qun Li,Zhihui Hao,Xucai Zheng,Wei He
We report a novel water-soluble polysaccharide from Rhizoma panacis japonica, namely, PJ-1 with anti-inflammatory activity. We first obtained a polysaccharide from this herb by eluting with water. After fully characterizing PJ-1 with a series of chromatographic technologies, we evaluated its biological activity by stimulating Raw 264.7 cells to express inflammatory cytokines and found that PJ-1 effectively enhanced the production of anti-inflammatory factors such as IL-10. We further identified its anti-inflammatory effect in a mouse model of sepsis induced by a lipopolysaccharide. The treatment of PJ-1 evidently suppressed the secretion of major inflammatory cytokines and increased the survival rate of mice. Particularly, we verified the STAT3 signal pathway responsible for the anti-inflammatory activity. Thus, PJ-1, which has remarkable anti-inflammatory effect and mechanism of action, may be a promising candidate as an anti-inflammatory agent.
研究领域:
药理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2024
·
IF 3.6
Xiao-Li Zheng,Zhi-Di Li,Kai-Zhi Luo,Yang-Ling Li,Ye-Han Liu,Shu-Ying Shen,Fei-Yan Shen,Wan-Yan Li,Guo-Qing Chen,Chong Zhang,Ling-Hui Zeng
Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2023
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IF 3.5
Wenbin Wang,Shiyang Zhou,Wenming Jiang,Guangying Chen
A series of 1-(2-oxocyclohexyl)butane-1, 3-dione derivatives were designed and synthesized as TLR4 inhibitors by modifying the core structure of the lead compound ((6, 8-dioxo-1, 2, 3, 4, 6, 7, 8, 8a-octahydronaphthalen-2-yl) carbamate)). In vitro , compound 3p significantly inhibited the proliferation of rat synovial cells, inhibited the proliferation of LPS-induced RAW264.7 cells, and inhibited TLR4 activity, with IC 50 values of 1.21 ± 0.09 μM, 0.73 ± 0.05 μM and 0.43 ± 0.03 μM, respectively, which was superior to the positive control methotrexate. In vivo anti-rheumatoid arthritis evaluation, compound 3p can significantly inhibit the inflammatory factors TNF-α, IL-1β and IL-6, so as to achieve the therapeutic purpose. In the preliminary mechanism study, compound 3p has obvious regulatory effects on the abnormal increase of TLR4, JAK2 and STAT3 protein and gene expression related to inflammatory signaling pathway in RAW264.7 cells. In summary, this study aims to develop more effective candidates for rheumatoid arthritis.
研究领域:
免疫学
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药理学
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医学
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DOI
PubMed
高影响因子
FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
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2025
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IF 2.2
Jianuo Li,Yuhuai Guo,Xiangxin Zeng,Hongzhao Tian,Yapeng Han,Shuo Cai,Min Sun
Introduction. The aberrant activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway is involved in spinal cord injury (SCI) progression. Electroacupuncture (EA) stimulation is effective in alleviating SCI, but the mechanism is poorly understood. Material and methods. An SCI model was constructed by cord contusion at T10, and AG490 (a JAK2 inhibitor) served as a positive control in this study. We evaluated the effects of EA on locomotor activity and spinal damage in SCI rats. The effects of EA on astrocytes and microglia and on the JAK2/STAT3 signalling pathway in the cells were investigated. Results. Behavioural tests showed that hind limb motor function of rats was improved after EA stimulation. The therapeutic effects of EA stimulation in restoring motor function, alleviating injured spinal cords, and inhibiting spinal cord neuronal apoptosis in SCI rats, were similar to those of AG490. Increased STAT3 activation was observed in astrocytes and microglia in the spinal cord of SCI rats, and this was reversed by EA stimulation. EA alleviated astrogliosis and inhibited microglia M1 polarisation in SCI rat spinal cords. In addition, RNA expression levels of pro-inflammatory factors IL-6, CXCL1, and TNF-α in rat spinal cords were suppressed by EA stimulation, while the expression level of the anti-inflammatory factor heme oxygenase 1 was increased. Meanwhile, the expression of p-JAK2, p-STAT3, and JAK2/STAT3 downstream targets SOCS3 and COX-2 in the spinal cord of SCI rats was inhibited by EA stimulation. Interestingly, the observed effects were comparable to those treated with EA. Conclusions. Our findings demonstrate that EA stimulation ameliorates SCI in rats and exerts an inhibitory effect on the JAK2/STAT3 signalling pathway.
研究领域:
神经科学
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医学
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产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2021
·
IF 3.411
Xuehua Piao,Xiaodan Sui,Baohai Liu,Tingfang Cui,Zinan Qi
Picroside II is an important ingredient agent in Traditional Chinese medicine and hoped to reduce hepatocellular injury caused by severe acute pancreatitis (SAP). An SAP-induced hepatocellular injury model was established in rats by using pentobarbital sodium. 27 rats were divided into 3 groups: the sham group (SG), model group (MG), and Picroside groups (PG). SAP-induced hepatocellular injury was assessed using hematoxylin and eosin staining. We measured hepatocellular enzymes (amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)), oxidative stress factors (superoxidase dismutase (SOD) and malondialdehyde (MDA)), and inflammatory factors (tumor necrosis factor α (TNF-α), interleukin- (IL-) 6, and IL-10), apoptotic factors (BAX and cleaved caspase 3), and inflammatory signaling (Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), p-JAK2, and p-STAT3) in hepatocellular tissues. The SAP-induced hepatocellular injury model was successfully established. Picroside II treatment repaired hepatocellular injury by reducing the activities of AMY, ALT, and AST; reducing the levels of MDA, TNF-α, IL-1, IL-6, p-JAK2, p-STAT3, BAX, and cleaved caspase 3; and increasing the levels of SOD and IL-10. Picroside II exerted protective function for the SAP-induced hepatocellular injury model. Picroside II improved SAP-induced hepatocellular injury and antioxidant and anti-inflammatory properties by affecting JAK2/STAT3 phosphorylation signaling.
研究领域:
药理学
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分子生物学
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传统中药研究
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DOI
PubMed
高影响因子
BMC Pulmonary Medicine
·
2024
·Vol. 24
·期 1
·1-16
·
IF 2.6
Sun Lili,Liu Lihua,Liang Dongxue,Liu Linlin
Pulmonary hypertension (PH) is a chronic pulmonary vascular disease and causes massive deaths. Here, we intended to investigate the function and mechanism of SOCS5 in PH. We engineered a hypoxia-induced PH model in mice. HE staining were implemented to evaluate pathological alterations in the lung tissues. The potential mechanism of SOCS5 in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was explored in vitro. RT-qPCR and western blot revealed that the level of SOCS5 was decreased both in PH mice and hypoxia-induced HPASMCs. Functional assays were performed for confirming the role of SOCS5 in modulating the cell phenotype and JAK2/STAT3 pathway in HPASMCs. Results revealed that overexpression of SOCS5 suppressed proliferation, migration and contraction of HPASMCs and negatively regulated the JAK2/STAT3 signaling pathway in HPASMCs under hypoxia in vitro, while knockdown of SOCS5 accelerated it. As evidenced by mechanism studies, SOCS5 was targeted and regulated by miR-155-5p, hence affecting on HPASMC proliferation, migration and contraction. These outcomes indicated that the decreased level of SOCS5 in hypoxia-induced HPASMCs promoted the cell proliferation, cell migration, and cell contraction through activating JAK2/STAT3 signaling pathway. Moreover, SOCS5 was targeted by miR-155-5p. All in all, our work hinted that miR-155-5p/SOCS5/JAK2/STAT3 axis played a crucial part in PH.
研究领域:
心血管疾病
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分子生物学
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细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Daermu Qumu,Mu Tian,Hengxi Li,Xiujuan Yang,Binhui Han,Lanting Wei,Bo Li,Mengxue Ma,Junjie He,Xiaoni Shao
Galangin (GAL), a flavonol found in Alpinia officinarum and propolis, is a promising functional food. This study investigated the therapeutic effects and mechanisms of GAL in mice with hyperuricemic nephropathy (HN) by focusing on renal metabolomics and network pharmacology. In this study, we conducted untargeted metabolomic analysis and network pharmacology prediction. Subsequently, a compound-reaction-enzyme-gene network was constructed based on the results of metabolomics and network pharmacology to elucidate potential connections. The results demonstrated that GAL can improve renal interstitial fibrosis and inflammatory infiltration and reduce serum levels of uric acid (UA), urea nitrogen (UREA), and creatinine (CREA). Metabolome analysis indicated that GAL affected thiamine, pyrimidine, nicotinate, nicotinamide, pyruvate, glyoxylate, and dicarboxylate metabolism. Network pharmacology and experimental results showed that GAL reduced the key target expression of the tumor protein P53 (TP53), tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), heat shock protein 90 alpha family class A member 1 (HSP90aa1), albumin (ALB), and caspase-3 (CASP3). GAL also downregulated the expression of Janus kinase 2 (JAK2), phospho-JAK2 (P-JAK2), and phospho-STAT3 (P-STAT3). Furthermore, a joint analysis of the metabolome and network pharmacology showed that GAL can reverse HN through amino acid metabolism, nucleotide metabolism, energy metabolism, and endocrine system pathways. GAL can alleviate HN effectively and might play synergistic therapeutic roles through regulating metabolic profiles and the JAK2/STAT3 signaling pathway.
研究领域:
医学
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药理学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Wenli Guo,Jinjin Zhang,Xiaoqian Zhang,Quanzhong Ren,Guangzhe Zheng,Jianxin Zhang,Guoxing Nie
Cadmium (Cd) pollution is considered a pressing challenge to eco-environment and public health worldwide. Although it has been well-documented that Cd exhibits various adverse effects on aquatic animals, it is still largely unknown whether and how Cd at environmentally relevant concentrations affects iron metabolism . Here, we studied the effects of environmental Cd exposure (5 and 50 μg/L) on iron homeostasis and possible mechanisms in common carp. The data revealed that Cd elevated serum iron, transferrin saturation and iron deposition in livers and spleens, leading to the disruption of systemic iron homeostasis. Mechanistic investigations substantiated that Cd drove hemolysis by compromising the osmotic fragility and inducing defective morphology of erythrocytes. Cd concurrently exacerbated hepatic inflammatory responses, resulting in the activation of IL6-Stat3 signaling and subsequent hepcidin transcription. Notably, Cd elicited ferroptosis through increased iron burden and oxidative stress in livers. Taken together, our findings provide evidence and mechanistic insight that environmental Cd exposure could undermine iron homeostasis via erythrotoxicity and hepatotoxicity. Further investigation and ecological risk assessment of Cd and other pollutants on metabolism-related effects is warranted, especially under the realistic exposure scenarios.
研究领域:
环境科学
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毒理学
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水生生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 12
·期 1
·88
·
IF 7.675
Shuo Han,Lifu Chen,Yi Zhang,Shihui Xie,Jiali Yang,Songkun Su,Hong Yao,Peiying Shi
Bee pollen possesses an anti-cardiomyocyte injury effect by reducing oxidative stress levels and inhibiting inflammatory response and apoptosis, but the possible effect mechanism has rarely been reported. This paper explores the effect of the extract of lotus bee pollen (LBPE) on cardiomyocyte hypertrophy (CH) and its mechanism. The main components of LBPE were identified via UPLC-QTOF MS. An isoproterenol-induced rat H9c2 CH model was subsequently used to evaluate the protection of LBPE on cells. LBPE (100, 250 and 500 μg∙mL−1) reduced the surface area, total protein content and MDA content, and increased SOD activity and GSH content in CH model in a dose-dependent manner. Meanwhile, quantitative real-time PCR trials confirmed that LBPE reduced the gene expression levels of CH markers, pro-inflammatory cytokines and pro-apoptosis factors, and increased the Bcl-2 mRNA expression and Bcl-2/Bax ratio in a dose-dependent manner. Furthermore, target fishing, bioinformatics analysis and molecular docking suggested JAK2 could be a pivotal target protein for the main active ingredients in the LBPE against CH. Ultimately, Western blot (WB) trials confirmed that LBPE can dose-dependently inhibit the phosphorylation of JAK2 and STAT3. The results show that LBPE can protect against ISO-induced CH, possibly via targeting the JAK2/STAT3 pathway, also suggesting that LBPE may be a promising candidate against CH.Keywords:lotus bee pollen extract;cardiomyocyte hypertrophy;JAK2/STAT3 signaling pathway;oxidative stress;inflammation
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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