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[Expressions of Bim and ERKs in multidrug-resistant hepatic carcinoma cells]
Feng Yan1, Xiaomin Wang, Quanming Ma
1Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.E-mail: yanfeng@xmzsh.com.
Objective:
To investigate the expressions of extracellular signal-regulated kinase (ERK) and the BH3-only subgroup of Bcl-2 related proteins (Bim) in multidrug-resistant hepatocellular carcinoma (HCC) cells and their association with drug resistance in the cells.
Methods:
The multdrug-resistant HepG-2 cell line was established by treatment with gradually increasing doses of ADM. CCK-8 assay was used to determine the drug sensitivity of the cells, and the expressions of MRP-1, P-gp, ERK1, ERK2, ERK5, and Bim were detected with Western blot. Bim mRNA expression level was measured using quantitative real-time PCR.
Results:
The drug resistance indices to ADM, 5-FU and CDDP was 6.8, 4.10, and 4.5 in HepG-2/ADM cells, respectively. The drug-resistantcells showed marked up-regulation of MRP-1, P-gp, ERK1, ERK2 and ERK5 with down-regulated phosphorylated ERK2 protein expression but no significant changes in phosphorylated ERK1 protein expression to result in a decreased ratio of P-ERK1/2 and P-ERK1/2. Bim mRNA and protein expressions were both decreased in HepG-2/ADM cells.
Conclusion:
ERK and Bim are related to multidrug resistance in HepG-2/ADM cells.
Insights
Extracellular signal-regulated kinase (ERK) and Bim expressions are linked to multidrug resistance in hepatocellular carcinoma (HCC) cells. Decreased Bim and altered ERK phosphorylation correlate with resistance, suggesting therapeutic targets for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) often develops multidrug resistance (MDR), limiting treatment efficacy.
- Understanding the molecular mechanisms underlying HCC drug resistance is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the expression of extracellular signal-regulated kinase (ERK) and Bim in multidrug-resistant HCC cells.
- To determine the association between ERK and Bim expression and drug resistance in HCC.
Main Methods:
- Established a multidrug-resistant HepG-2 cell line (HepG-2/ADM) using Adriamycin (ADM).
- Assessed drug sensitivity using CCK-8 assays.
- Quantified expressions of MRP-1, P-gp, ERK1, ERK2, ERK5, and Bim via Western blot and quantitative real-time PCR.
Main Results:
- HepG-2/ADM cells exhibited resistance to ADM, 5-FU, and CDDP.
- Upregulation of MRP-1, P-gp, ERK1, ERK2, and ERK5 was observed.
- Decreased Bim mRNA and protein levels, along with altered ERK phosphorylation patterns, were noted.
Conclusions:
- ERK and Bim play a significant role in the development of multidrug resistance in HepG-2/ADM cells.
- These findings suggest ERK and Bim as potential therapeutic targets for overcoming drug resistance in HCC.
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