MDR-reversing Effect of (-)epigallocatechin-3-gallate on Human MDR Cell Lines KBV200

Objective 　Experiment s were carried out to examine the potential of EGCG(epigallocatechingallate) as a multidrug resistance (MDR) reversal agents. Methods 　MTT assay was used to detect cytotoxicity of EGCG and vincristine (VCR) . Int racellular concent ration of VCR was detected by high performance liquid chromatograghy( HPLC) . Flow cytomet ry was used to determine the expression of P-gp.In a BALB/ C-nu/ nu mouse model, cells of drug-sensitive KB and KBV200 (MDR) cell lines were inoculated to yield tumors in opposite flanks. EGCG and VCR were injected to the peritoneal of nude mice with carcinoma xenograf t s. MDR1 mRNA expression was observed with reverse-transcriptase PCR. Results 　Survival of cells incubated with EGCG at 75 mg/ l for 72 h was over 80 %. EGCG at 8 mg/ l almost completely reversed resistance to VCR in KBV200 cells and produced a 13. 0-fold reversal of MDR. It increased int racellular concent ration of VCR in KBV200 cells while not influence that in KB cells. In KBV200 xenograf t model, neither EGCG nor VCR inhibited tumor growth. However, VCR and EGCG combined inhibited tumor growth by 72. 8 %. EGCG inhibited MDR1 expression and augmented accumulation of VCR in KBV200 cells. Conclusion 　The result s suggest that EGCGis a potent MDR-reversing agent in vit ro and in vivo. The mechanism is probably associated with down-regulating the expression of MDR1 and P-gp . So that increases the concent rations of anticancer drug in tumor cells.