Reversal Effect And Mechanism Of Apigenin On Drug Resistance In HCT116/L-OHP Cells

Chemotherapy is a very important treatment for colorectal cancers.However,the occurrence of drug resistance remains a major problem hindering successful cancer chemotherapy.Therefore,discovering a reversal agent might provide a new potential drug for colorectal cancer therapy.Apigenin is a non-mutagenic dietary flavonoid,and it could inhibite the expression of P-gp and bcl-2.We hope to clarify the reversal effect and mechanism of apigenin on drug resistance in HCT116/L-OHP cells.MTT assay was used to investigate the inhibition of apigenin on HCT116 and HCT116/L-OHP,and to investigate the reversal of apigenin on drug resistance of HCT116/L-OHP.The Rh123 concentration in cells and apoptotic rate were assayed by flow cytometry analysis.The influence of apigenin on P-gp and bcl-2 expression at mRNA level was detected by real-time RT-PCR.We used Elisa method to investigate the expression of P-gp,p-Akt,p-I?B?,I?B?,bcl-2,bax,caspase-3.Our results showed that 90?mol/L,50?mol/L,and 40?mol/L were the combined concentration of apigenin in 24 h,36h,48 h assays,and the reversal folds were 1.33,1.51,and 2.06,respectively.Compared to the resistant group,the Rh123 accumulation in resistant apigenin group was increased significantly(p<0.01).Compared with the resistant L-OHP group,after given apigenin,its apoptotic rate was increased significantly(p<0.05).Compared to the resistant group,the P-gp and bcl-2 mRNA expression level in resistant apigenin group were decreased significantly(p<0.01).The P-gp,bcl-2,p-Akt,p-I?B? expression in resistant group were lower than the resistant apigenin group,I?B? and caspase-3 expression were higher(p<0.05-0.01).In conclusion,given 40?mol/L apigenin for 48 h had the best reversal effect.Its mechanism may be related to inhibite the function of P-gp,to down-regulate expression of P-gp and bcl-2,to up-regulate bax and caspase-3,and to increase the apoptotic rate.