Dataset Information

Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells.

ABSTRACT: Glycochenodeoxycholate (GCDA), a toxic component in bile salts, is involved in carcinogenesis of gastrointestinal tumors. The objective of this research was to study the function of ERK1/2 in the GCDA-mediated survival and drug-resistance in hepatocellular carcinoma cells (HCCs). Firstly, extracellular signal-regulated kinase 1/2 (ERK1/2) was detected extensively expressed in liver cancer cells, and silencing ERK1/2 by RNA interference could suppress GCDA-stimulated survival and promote apoptosis. Furthermore, phosphorylation of endogenous ERK1/2 could be potently stimulated by GCDA in combination with enhanced chemoresistance in QGY-7703 hepatocellular carcinoma cells. The GCDA-mediated proliferation and chemoresistance could be impaired by PD98059, which acted as an inhibitor to block the phosphorylation of ERK1/2. Mechanistically, PD98059 was able to potently suppress GCDA-stimulated nuclear aggregation of ERK1/2 and p-ERK1/2, upregulate pro-survival protein Mcl-1 and downregulate pro-apoptotic protein Bim. The results of this study indicated that disruption of ERK1/2 by blocking phosphorylation or nuclear translocation may put forward new methods for solving the problem of GCDA-related proliferation and drug-resistance in liver cancer treatment.

SUBMITTER: Li B

PROVIDER: S-EPMC8313996 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells.

Li Bingxin B Zhou Maojun M Wang Jue J Xu Hongjuan H Yang Manyi M

Frontiers in oncology 20210713

Glycochenodeoxycholate (GCDA), a toxic component in bile salts, is involved in carcinogenesis of gastrointestinal tumors. The objective of this research was to study the function of ERK1/2 in the GCDA-mediated survival and drug-resistance in hepatocellular carcinoma cells (HCCs). Firstly, extracellular signal-regulated kinase 1/2 (ERK1/2) was detected extensively expressed in liver cancer cells, and silencing ERK1/2 by RNA interference could suppress GCDA-stimulated survival and promote apoptosi ...[more]

PMID: 34327135

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Project description:Hepatocellular carcinoma(HCC) has a high mortality and morbidity rate and seriously jeopardizes human life. Chemicals and chemotherapeutic agents have been experiencing problems such as side effects and drug resistance in the treatment of HCC, which cannot meet the needs of clinical treatment. Therefore, finding novel low-toxicity and high-efficiency anti-hepatocellular carcinoma drugs and exploring their mechanisms of action have become the current problems to be solved in the treatment of HCC. Several studies have reported anticancer effects of inotodiol. This study focuses on the anticancer effect of inotodiol in HCC cells and its molecular mechanism, aiming to explore its anticancer effect in depth. The CCK8 assay was utilized to assess cell viability, the scratch assay was utilized to detect migration ability, the clone formation assay was utilized to detect clonogenic ability, and flow cytometry was utilized to analyze apoptosis and cell cycle. Animal experiments was utilized to verify the inhibitory effect of inotodiol on HCC. Meanwhile, western blotting was utilized to detect proteins associated with apoptosis, cell cycle and MAPK/ERK pathway. These results showed that inotodiol has the ability to promote apoptosis, as well as inhibit the ability of cell proliferation, migration, and clonogenic ability. The cell cycle was arrested in G1 phase, when the expression of CDK2, CDK4, CDK6 and Cyclin D were inhibited. In addition, inotodiol showed to induce apoptosis, characterized by an increase in Bax expression, a decrease in Bcl-2, Bcl-XL and MCL1 expression, the initiation of cleaved PARP1 and cleaved caspase 3, and inhibition of the MAPK/ERK pathway. Animal studies demonstrated that inotodiol possessed the ability to suppress tumor growth in nude mice models, at the same time, there was no significant impact on the body weight and organs of the mice. In conclusion, the findings presented herein compellingly suggest that inotodiol may serve as a promising candidate for the treatment of hepatocellular carcinoma (HCC).

Dataset Information

Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells.

Publications

Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells.

Similar Datasets

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