High Phosphorylation Of P³⁸ MAPK In Drug Resistant Hepatocellular Carcinoma Cell Lines And Its Significance

Objective: To investigat the effect and significance of P38MAPK phoshohrylation in drug-resistance hepatocellular carcinoma cell lines.Method: A CDDP-resistant human hepatocellular carcinoma cell line was obtained from HepG2 by gradient anti-cancer drug induced method. At each time point,the expression of p38MAPK phosphorylation was detected by western blotting in the HepG2/CDDP kinetic drug resistance mode which was established in 2.0mg/L CDDP. At the same time, the HepG2/CDDP kinetic drug resistance mode was treated with P38MAPK inhibitor SB203580. Then, IC50 were observed by MTT assay;the cell cycle was evaluated by flow cytometry assay;The expression levels of P-gp,Bcl-2,Bax,cyclinD1 and JNK phosphorylation were evaluated by western blotting.Results: The resistance index of HepG2/CDDP was 6.8 and The kinetic drug resistance model was successfully established.The model was moderate resistance to CDDP .The expression levels of p38MAPK phosphorylation was progressively increased in the HepG2/CDDP. Compared with the control group, in the treatment group which was treated with P38MAPK inhibitor SB203580, The IC50, the proportion of G0/G1 stage cells, the expressionslevels of Bcl-2 and P-gp were lower, while the expressionslevels of bax, cyclinD1 and JNK phosphorylation were higher.Conclusions: In HepG2/CDDP kinetic drug resistance model, increased P38MAPK phosphorylation could promote the drug resistance phenotype of hepatocellular carcinoma cells. Repress the activation of P38MAPK can reverse the drug resistance phenotype of hepatocellular carcinoma cells.