The Reversal Effects of Trametes Robiniophila Murr. on Multidrug Resistance in Resistant Human Hepatocellular Carcinoma Cell Line BEL-7402/5-Fu

Purpose To evaluate the reversal effect of Trametes robiniophila Murr. on multidrug resistance in drug resistant human hepatocellular carcinoma cell line BEL-7402/5-Fu,and explore its mechanism. Methods The growth inhibition of BEL-7402/5-Fu cell and the reversal effects of Trametes robiniophila Murr. were measured by MTT assay. Intracelluar accumulation of doxorubicin and rhodamine-123 were detected by flow cytometry (FCM). The mRNA expressions of MDR1,ABCG2 and LRP were detected by RT-PCR. The expression of P-gp was detected by Western Blot.Results The IC 50 of chemotherapeutics agents in BEL-7402/5-Fu cells decreased obviously by adding non-cytotoxic concentration of Trametes robiniophila Murr. Reversal fold (RF) of Trametes robiniophila Murr. on 5-Fu,EPI and PTX were 3.67-fold,2.38-fold and 2.16-fold,respectively,and relative reversal rate (RRR%) were 72.8%,70.1% and 74.9%, respectively. FCM results showed that both Trametes robiniophila Murr. significantly enhanced intracelluar accumulation of doxorubicin and rhodamine-123 compared to the control in BEL-7402/5-Fu cells. RT-PCR results showed that the mRNA expression level of MDR1 decreased significantly after treated with Trametes robiniophila Murr. compared to the control in BEL-7402/5-Fu cells,while the mRNA expression levels of ABCG2 and LRP are not significantly changed. Western blot showed P-gp protein expression level was decreased in BEL-7402/5-Fu cells after treated with Trametes robiniophila Murr. Conclusions Trametes robiniophila Murr. can partially reverse MDR by down-regulating the mRNA and protein expression levels of MDR1/P-gp,inhibiting the function of P-gp and enhancing intracelluar accumulation of chemotherapeutic agents in human hepatocellular carcinoma in vitro. The reversal effect of Trametes robiniophila Murr. on MDR may be irrelevant to ABCG2 and LRP.