Inhibitor of XIAP Embelin reverses the resistance of human pancreatic carcinoma Patu8988 cell line to pemetrexed

Abstract

Objective To investigate whether safe doses of Embelin, a small-molecular weight inhibitor of X-linked inhibitor of apoptosis protein (XIAP) can reverse the resistance of human pancreatic carcinoma Patu8988 cell line to pemetrexed. Methods The effect of Embelin on growth inhibition of pemetrexed-resistant Patu8988 strain and its parent strain and half maximal inhibitory concentration ( IC50 ) of pemetrexed alone and its combination with Embelin for the growth of the two cell strains were determined by the cell counting Kit-8 assay. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the changes in the expression of XIAP mRNA and protein after the interference of Embelin. Results Embelin presented growth inhibition on both cell stains without significant differences in vitro in a dose-dependent manner. The maximal safe dose of Embelin for both strains was 2. 5 mg/L. Only in Patu8988 strain to pemetrexed was noted a significant difference in the IC50 value between pemetrexed alone and pemetrexed in combination with safe doses of Embelin. The expression of XIAP mRNA and protein was decreased by 33% and 25% respectively (P＜0. 05) in pemetrexed-resistant Patu8988 strain after the interference of Embelin. Flow cytometry analysis showed that the apoptosis rate of drug-resistant cells treated with pemetrexed in combination with Embelin was higher than that of cells treated with pemetrexed alone [ (38.73±2.55)% vs (25. 87 ±2.81)%, P＜0.05]. Conclusion Embelin can reduce the the higher expression of XIAP mRNA and protein levels in drug-resistant cells and increase the sensitivity of drug-resistant Patu8988 cell strain to pemetrexed, but has no significant effect on parental Patu8988 strain. Key words: Pancreatic carcinoma; Drug resistance; Embelin; Reverse