The regulatory mechanism of JNK signal transduction pathway-mediated multidrug-resistance in human hepatic cancer cell line Bel-7402/FU
10.3781/j.issn.1000-7431.2014.01.004
- Author:
Can HUANG
1
Author Information
1. Department of Pharmacy, Anhui Medical University
- Publication Type:Journal Article
- Keywords:
Bel-7402/5-FU cells;
JNK signal pathway;
Liver neoplasms;
Multidrug-resistance-associated proteins
- From:
Tumor
2014;34(1):19-25
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the regulatory effect of C-Jun N-terminal kinase (JNK) signal transduction pathway on multi-resistance in the human hepatic cancer Bel-7402/5-fluorouracil (FU) cells, and provide a possible novel target for study on the mechanism of multidrug-resistance in human hepatic cancer cells. Methods: The protein expression levels of JNK and phospho-JNK (p-JNK) in parental human hepatic cancer Bel-7402 cells and the drug-resistant Bel-7402/FU cells were detected by Western blotting. After the inhibition of JNK pathway induced by specific inhibitior SP600125, the expressions of multi-drug resistance 1 (MDR1) mRNA and P-glycoprotein (P-gp) in Bel-7402/FU cells were detected by RT-PCR and immunocytochemistry, respectively. The accumulation and efflux of rhodanmine 123 (Rh123) in the cells were examined by flow cytometry, and the sensitivity to 5-FU of Bel-7402/FU cells was detected by MTT method. Results: The expression of JNK protein was not significantly different between the Bel-7402/FU cells and the parental Bel-7402 cells, but the expression of p-JNK protein in the Bel-7402/FU cells was significantly increased. After inhibition of JNK pathway, the expressions of MDR1 mRNA and P-gp protein were obviously decreased, with a markedly increased accumulation and decreased efflux of Rh123, leading to enhhanced sensitivity to 5-FU of Bel-7402/FU cells. Conclusion: JNK signal transduction pathway is involved in the expressions of MDR1 gene and P-gp in drug-resistant human hepatic cancer Bel-7402/FU cells, and it can regulate the sensitivity to 5-FU of Bel-7402/FU cells.
