MDR-reversing effect of P15 to multidrug-resistant hepatocellular carcinoma cells
AIM: To investigate the P15 expression level in HepG2/CDDP kinetic multidrug-resistant (MDR) models and its possible molecular mechanism in muhidrug-resistant hepatocelhlar carcinoma cells. METHODS: Anti-cancer drug induced method was used to construct the HepG2/CDDP kinetic MDR models and RT-PCR and Western blot were used to detect the P15 expression in HepG2/CDDP kinetic MDR models. PI5 over-expressed HepG2/CDDP-P15 cell line and its empty vector control HepG2/CDDP-PC cell line were constructed. Flow cytometry(FCM) was used to study the cell cycle distribution, adriamycin(ADR) accumulation and detention in HepG2/CDDP-P15 cells and its control cell lines, and classic MDR molecules-P-gp and MRP-1 were examined by Western blot. RESULTS: The HepG2/CDDP kinetic MDR model was successfully established. The mRNA level of P15 decreased with the increasing drug resistance of hepatocelhlar carcinoma cells. Up-regulation of expressions of P15 in HepG2/CDDP cells inhibited the cell proliferative activity, decreased the ability of the drug transports, increased ADR accumulation and retention. CONCLUSION: Up-regulating PI5 reverses the MDR phenotype of hepatecellular carcinoma cells by down-regulating the P-gp and MRP-1 expressions.
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万方数据
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