Food Science and Human Wellness
·
2023
·
IF 7
Zhenhua Liu,Mengke Wang,Lijun Meng,Yixiao Chen,Qiuyi Wang,Yan Zhang,Xuefeng Xi,Wenyi Kang
Patrinia scabiosaefolia , is used as wild vegetable in China for more than 2 000 years, with a variety of pharmacological activities, including anti-inflammatory, anti-tumor and hypoglycemic. Based on our ongoing research on chemical constituents and hypoglycemic activity of P. scabiosaefolia , 4 lignan compounds, (+)-isolariciresinol ( 1 ), 7 R ,7' R ,8 S ,8' S -(+)-neo-olivil-4- O - β - D -glucopyranoside ( 2 ), 4- O- methylcedrusin ( 3 ) and patrinian A ( 4 ), were isolated and identified. The hypoglycemic activity showed that compounds 2 and 3 could extremely significantly improve insulin resistance at 100 ( P < 0.001), 50 ( P < 0.001) and 25 µmol/L ( P < 0.01) in IR 3T3-L1 cells. While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100 µmol/L ( P < 0.01). Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS, PI-3K, p-AKT and glucose transporter 4 (GLUT4), and promoted the transcription of GLUT4 mRNA. Therefore, the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.
研究领域:
药理学
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分子生物学
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内分泌学
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DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-15
·
IF 3.9
Xia Hong,Tai Xue-jiao,Cheng Wang,Wu Yi,He Dan,Wang Li-feng,Liu Hao,Zhang Shen-yi,Sun Yu-ting,Liu Hang-zhi,Liu Dan-dan,Zhao Hu-zi,Ji Fu-yun,Li Xi-hua
Small cell lung cancer (SCLC) is a therapeutically challenging disease. Metformin, an effective agent for the treatment of type 2 diabetes, has been shown to have antitumour effects on many cancers, including non-small cell lung cancer (NSCLC) and breast cancer. Currently, the antitumour effects of metformin on SCLC and the underlying molecular mechanisms remain unclear. CCK-8, EdU, colony formation, flow cytometry, immunofluorescence, molecular docking, western blotting, nude mouse transplanted tumour model, and immunohistochemistry experiments were conducted to analyse gene functions and the underlying mechanism involved. In vitro experiments demonstrated that metformin inhibited the growth of SCLC cells (H446, H526, H446/DDP and H526/DDP), which was confirmed in xenograft mouse models in vivo. Additionally, metformin induced cell cycle arrest, apoptosis, and autophagy in these SCLC cells. The molecular docking results indicated that metformin has a certain binding affinity for EGFR. The western blotting results revealed that metformin decreased the expression of EGFR, p-EGFR, AKT, and p-AKT, which could be reversed by EGF and SC79. Moreover, metformin activated AMPK and inactivated mTOR, and compound C and SC79 increased the levels of p-mTOR. Metformin can not only enhance the antitumour effect of cisplatin but also alleviate the toxic effects of cisplatin on the organs of xenograft model animals. In summary, the current study revealed that metformin inhibits the growth of SCLC by inducing autophagy and apoptosis via suppression of the EGFR/AKT/AMPK/mTOR pathway. Metformin might be a promising candidate drug for combination therapy of SCLC.
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
Biomaterials Science
·
2019
·Vol. 7
·期 12
·5054-5067
·
IF 5.251
Tiantian Zuo,Jing Li,Jun Zhang,Liang Sun,Xiao Liang,Jie Yang,Qi Shen
As the principal reason for the inducement of high mortality, tumor metastasis is regulated by different pathways owing to its complexity and multistep process. In order to inhibit the proliferation and metastasis of human breast cancer simultaneously, controlling the codelivery of chemotherapeutics and pathway inhibitors precisely has been considered as a high-potential strategy to accurately eliminate tumor metastasis. In this study, polymer PLGA-p-PEI-DA was synthesised and automatically assembled into a cascade “trinity” response drug delivery system, i.e., PPP-DA/NPs (PLGA: poly(lactin-co-glycolic acid), PEI: polyethyleneimine, DA: 2,3-dimethylmaleic anhydride). In the tumor microenvironment, PPP-DA/NPs could remove the outer DA molecules via the pH-sensitive hydrolysis of β-carboxylic amide bonded with DA and PEI. Then, PPP-DA/NPs were broken up owing to the enzymatically cleavable GFLGF (Gly-Phe-Leu-Gly-Phe) linker. The structure of the polymer and the properties of PPP-DA/NPs were evaluated in detail. Moreover, studies on the antitumor metastasis efficiency and antitumor mechanism of PPP-DA/NPs were carried out in detail. As demonstrated in this study, PPP-DA/NPs could reverse the potential in pH 6.8 PBS and showed elevated cellular uptake efficiency. Moreover, PPP-DA/NPs exhibited strong antitumor metastasis ability in vitro and in vivo. The tumor inhibiting rate (TIR) of PPP-DA/NPs (68.4%) was significantly higher than that of docetaxel (DTX) (5.9%). The antitumor mechanistic studies confirmed that PPP-DA/NPs could down-regulate the expressions of Akt, MMP-9 and pro-caspase-3/9 protein, as indicated by western blot analysis. This multifunctional drug delivery system (DDS) is highly selective and effective in inhibiting tumor metastasis, which shows a great potential in inventing smart nanocarriers for targeted tumor-metastasis therapy.
研究领域:
肿瘤学
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药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yunzhi Liu,Cuicui Huang,Min Luo,Wenfu Lu,Baifeng Zhang,Lu Bai,Shuyue Zheng,Yanan Tan,Shanshan Li,Huali Wang,Lanqi Gong,Xinyuan Guan
Nasopharyngeal carcinoma (NPC) is one of the common head and neck cancers in Southern China and Southeast Asia. Although current studies have adequately characterized the tumor microenvironment (TME) of NPC, little attention has been paid to how cell-cell interactions within the TME promote tumorigenesis. In this study, it is found that C1q + tumor-associated macrophages (TAMs) are significantly enriched in NPC tumors. Moreover, both enriched C1q + TAMs and elevated C1q expression are associated with the progression and poor prognosis in NPC patients. In vitro and in vivo studies demonstrate that C1q directly boosts the malignancy and stemness of tumor cells. Mechanistically, C1q activates the Phosphatidylinositol-3-kinase (PI3K)/AKT pathway through interacting with GPR17, a member of the G protein-coupled receptor family, thereby inducing DNA hypermethylation of tumor cells to promote tumor development. It is further proved that DNA hypermethylated NPC cells induced by C1q elicited the immunosuppressive phenotype of TAMs. Targeted blockade of C1q with a neutralizing antibody restricts NPC progression in the humanized mouse model. It is assumed that the differentiation of C1q + TAMs possibly acquired both M1 and M2 polarization conditions. These findings provide new insights into the cellular communication in the TME of NPC and may have important applications for the development of new targeted therapies.
研究领域:
肿瘤学
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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
Toxicology Research
·
2024
·Vol. 13
·期 1
·
IF 2.2
Zhang Chu,Liao Yupei,Li Tangjia,Zhong Haijing,Shan Luchen,Yu Pei,Xia Chenglai,Xu Lipeng
The 2022 US Cancer Statistics show that breast cancer is one of the most common cancers in women. Epidemiology has shown that adding flavonoids to the diet inhibits cancers that arise in particular women, such as cervical cancer, ovarian cancer, and breast cancer. Although there have been research reports on apigenin (API) and breast cancer, its anti-tumor effect and potential mechanism on breast cancer have not yet been clarified. Therefore, in this study, we used 4T1 cells and a 4T1 xenograft tumor mouse model to investigate the antitumor effect of API on breast cancer and its underlying mechanism. In vitro, we used MTT, transwell, staining, and western blotting to investigate the inhibitory effect of apigenin on 4T1 and the underlying molecular mechanism. In vivo by establishing a xenograft tumor model, using immunohistochemistry, and flow cytometry to study the inhibitory effect of apigenin on solid breast tumors and its effect on the tumor immune microenvironment. The results showed that API can induce breast cancer cell apoptosis through the PI3K/AKT/Nrf2 pathway and can improve the tumor immune microenvironment in mice with breast tumors, thereby inhibiting the growth of breast cancer. Thus, API may be a promising agent for breast cancer treatment.
研究领域:
肿瘤学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Yasi Mo,Yong Wu,Xin Li,Hui Rao,Xianxiang Tian,Danni Wu,Zhenpeng Qiu,Guohua Zheng,Junjie Hu
Hepatocellular carcinoma (HCC) is one of the most common fatal malignancies worldwide. Inhibition of the lipogenic enzymes involved in hepatic de novo lipogenesis can both effectively restrain proliferation of HCC cells in vitro and reduce the risk of hepatocarcinogenesis in vivo . Although a natural coumarin derivative osthole shows efficacy in suppressing cell proliferation and inducing apoptosis in cultured hepatoma cells and HCC xenograft tumors, the molecular mechanism by which osthole delays hepatocellular malignant transformation during lipogenesis-driven hepatocarcinogenesis remains unknown. Here, we evaluate the efficacy of osthole in a rapid HCC mouse model featuring excessive levels of hepatic steatosis established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Moreover, human hepatoma cell lines were employed for in vitro assessment. Hematoxylin and eosin staining , immunoblotting and immunohistochemistry were applied for mechanistic investigations. The results revealed that if osthole was administered in the early stage of AKT/c-Met-driven HCC, it led to disease stabilization. Moreover, osthole alleviated hepatic steatosis in the AKT/c-Met mice. Further evidence at the molecular level suggested that osthole reduced the expression of phosphor-extracellular signal-regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA) and Ki67 in livers of the AKT/c-Met mice. Mechanically, osthole efficiently repressed the phospho-AKT (Thr308) / ribosomal protein S6 (RPS6) / fatty acid synthase (FASN) signaling both in mice and in vitro . Altogether, this study suggests that osthole exerts its antilipogenic and antiproliferative efficacy by suppressing the AKT/FASN axis and ERK phosphorylation, which contributes to its capacity to delay hepatocarcinogenesis.
研究领域:
癌症研究
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分子生物学
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药理学
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肝病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Jia-Qi He,Min-Xia Zheng,Hua-Zhong Ying,Yu-Sen Zhong,Huan-Huan Zhang,Min Xu,Chen-Huan Yu
Two polysaccharides (PRP1 and PRP2) were isolated from Platycodonis Radix . Preliminary structural analysis indicated that PRP1 was composed of glucose, fructose, and arabinose in a molar ratio of 1:1.91:1.59 with a molecular weight of 440 kDa, whereas PRP2 was composed of arabinose, fructose, and galactose in a molar ratio of 1:1.39:1.18 with a molecular weight of 2.85 kDa. Compared with PRP2, PRP1 exerted stronger anticancer activity in vitro. Treatment with 5–30 μg/ml of PRP1 significantly inhibited the proliferation of HepG2 cells in vitro, and oral administration at the doses of 75–300 mg/kg also reduced the tumor growth in vivo. The miRNA expression patterns of human liver cancer cells HepG2 in vivo under PRP1 treatment were established, and microRNA-21 (miR-21) as the onco-miRNA was appreciably downregulated. PRP1 repressed the expression of miR-21, which directly targeted and suppressed PTEN (a negative regulator of the PI3K/Akt signaling cascade), and subsequently upregulated the expression of PTEN but downregulated the PI3K/AKT pathway, thereby promoting liver cancer cell apoptosis. These findings indicated that PRP1 inhibited the proliferation and induced the apoptosis of HepG2 mainly via inactivating the miR-21/PI3K/AKT pathway. Therefore, PRP1 could be used as a food supplement and candidate for the treatment of liver cancer.
研究领域:
药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2021
·
IF 4.24
Yonglu Li,Yiru Zhang,Yaxuan Wang,Xin Yu,Ting Yu,Xiaodong Zheng,Qiang Chu
With high morbidity and mortality, non-small cell lung cancer (NSCLC) has become a challenge for humans, because its clinic chemotherapies still remain unsatisfactory. In this study, the leaf part of a traditional Chinese plant, Tetrastigma hemsleyanum (TL), was studied, and its main flavones compounds were extracted and purified (TLF), which were composed of 5-caffeoylquinic acid, 3-caffeoylquinic acid, 4-caffeoylquinic acid, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside. To study the anti-NSCLC ability of TLF, in vitro and in vivo studies were done. TLF inhibited the proliferation and migration of A549 cells and caused mitochondrial dysfunction. TLF significantly suppressed the tumor weight and volume, and down-regulated Ki67, proliferation cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) productions. To determine the intrinsic mechanism, proteins alternations were measured in solid tumors, and results showed that TLF blocked the Akt/mTOR pathway, and thereby induced autophagy, triggering Bcl and Caspase-dependent pathways, resulting in A549 cells’ apoptosis. This study indicated that TLF is a potential candidate to be an anti-NSCLC drug, or a supplementary resource for chemotherapy.
研究领域:
肿瘤学
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药理学
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分子生物学
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中医药学
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产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Min Chen,Xiaodong Wang,Bo Hu,Jian Zhou,Xin Wang,Wei Wei,Hua Zhou
Echinacoside is a natural ingredient with various pharmacological activities . In this study, we investigated the protective effects of echinacoside on cardiomyocytes (rat H9c2 cells) in an anoxia/reperfusion (A/R) model. Further, the regulatory function of sodium-calcium exchanger protein 3 (SLC8A3/NCX3) as well as the protein kinase B (AKT) signaling were studied. The present results indicated that echinacoside protected against A/R-induced apoptosis in a dose manner, which was characterized by a decrease in the apoptosis and caspase 3 protein levels in H9c2 cells. Further, Ca 2+ uptake were dose-dependently reduced in H9c2 cells by echinacoside under A/R conditions. Whereas, relative mRNA expression of SLC8A3 and protein levels of SLC8A3 and p-AKT showed opposite tendency. On the one hand, the A/R-induced abnormalities in H9c2 cells were remarkably ameliorated by activated p-AKT and over-expression of SLC8A3 but aggravated by inhibited p-AKT, and the aggravated effection were ameliorated by echinacoside. Moreover, protein levels of SLC8A3 were positively regulated by p-AKT signaling. On the other hand, apoptosis and Ca 2+ uptake as well as protein levels of caspase 3 were significantly increased by SLC8A3 silencing in H9c2 cells under normoxic conditions, and this symptom was remarkably reversed by echinacoside or Nimodipine (an antagonis of Ca 2+ ) treatment . Collectively, echinacoside has showed a cardioprotective effect against A/R treatment in a dose dependent manner in vitro, and this cardioprotective effect was potentially achieved via up-regulating p-AKT and SLC8A3.
研究领域:
药理学
·
心脏病学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BMC Nephrology
·
2019
·Vol. 20
·期 1
·1-7
·
IF 2.088
Xiong Ruifang,Lu Xiangxue,Song Jinghong,Li Han,Wang Shixiang
Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial.Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta.Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group).Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.
研究领域:
心血管疾病
·
分子生物学
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动物模型
·
信号转导
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2023
·Vol. 102
·期 1
·115-125
·
IF 3
Yan Zhang,Kun Dai,Dedong Xu,Hua Fan,Nannan Ji,Di Wang,Yunlu Zhao,Rui Liu
Saikosaponin A (SSA) has been revealed to have anti-breast cancer (BC) effect. However, the association between SSA and BC glycolysis is obscure. We want to probe the function and mechanism of SSA on BC glycolysis. Kaplan–Meier plotter revealed the relationship between STAT3 and the survival curve of BC. The protein kinase B (Akt)/signal transducer and activator of transcription 3 (STAT3) pathway and the viability in cells treated with or without 0, 5, 10, and 15 μM SSA were assessed by Western blot and cell counting kit-8. The biological behaviors, lactate, and ATP contents, glucose uptake, and Akt/STAT3 pathway-related markers in BC cells treated with colivelin or SSA were evaluated using cell function experiments, kit, and Western blot. Then, the impacts of colivelin and SSA on BC cells were tested again. The overexpressions of p-STAT3 and p-Akt in BC cells were weakened by 5, 10, and 15 μM SSA. Colivelin boosted the BC cell viability and proliferation and impeded apoptosis, while SSA did the opposite. Meanwhile, colivelin intensified lactate and ATP contents, glucose uptake, and Akt/STAT3 pathway-related markers level in BC cells, while SSA was the opposite. The modulation of SSA on the biological behavior, lactate and ATP productions, glucose uptake, and Akt/STAT3 pathway was rescued by colivelin. Our research unveiled new insights into SSA as a valuable candidate therapeutic agent for weakening glycolysis, and protruded the Akt/STAT3 pathway as a latent molecular target for SSA and glycolysis modulation.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2020
·Vol. 37
·期 2
·111-120
·
IF 1.737
Shi Liu,Ying Gong,Xue-Dong Xu,Hui Shen,Shuai Gao,Hai-Dong Bao,Shi-Bin Guo,Xue-Feng Yu,Jian Gong
Gastric cancer is one of the most common cancers globally and has a poor prognosis. MiR-936 has been reported to regulate cell activity and tumor progression in non-small cell lung cancer, glioma, and epithelial ovarian cancer. However, the specific role and mechanism of miR-936 in gastric cancer have not been explored. In present study, gastric cancer cells were transfected with miR-936 mimic, and cell proliferation, cell cycle distribution, cell apoptosis, migration and invasion were assessed via cell-counting kit-8, flow cytometry, wound healing, and transwell assay, respectively. Dual luciferase reporter assay was used to check miR-936 binding to its downstream target. It was shown that miR-936 was downregulated in gastric cancer tissues and cells. Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) was confirmed as a direct target of miR-936 and negatively regulated its expression by miR-936. Overexpression of miR-936 suppressed cell proliferation, cell cycle progression, cell migration and invasion, and enhanced cell apoptosis in gastric cancer cells, which could be reversed by further ERBB4 overexpression. Western blot results showed that miR-936/ERBB4 axis regulated Akt-related pathways to control gastric cancer cell activities. Therefore, our data suggest that miR-936 overexpression inhibits cell proliferation and invasion and promotes cell apoptosis through Akt-related pathways by targeting ERBB4, which provides novel insight to target miR-936 or miR-936/ERBB4 axis for the treatment of gastric cancer.
研究领域:
肿瘤学
·
分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）