Combination of tetrandrine and paclitaxel overcomes multidrug resistance on C6/MDR glioma cells / 中草药

ABSTRACT

Objective To investigate the feasibility of tetrandrine combined with paclitaxel (PTX) in multidrug resistance reversal on C6/MDR glioma cells, and explore the potential molecular mechanisms. Methods Through the comparison of non-resistant glioma C6 cells and drug-resistant glioma C6/MDR cells, the cytotoxicity of against C6/MDR (or C6) cells were assayed by MTT method. The intracellular accumulation of PTX and Rhodamine 123 (R123) were determined by high performance liquid chromatography (HPLC) and flow cytometry, respectively. The cell apoptosis induction of C6/MDR (or C6) cells was detected by AnnexinV-PE/7-AAD staining method after various intervention of PTX, tetrandrine, and PTX + HfA. P-glycoprotein (P-gp) expression and P-gp ATPase activity were evaluated through P-gp antibody binding assay kit and Pgp-GloTM assay systems, respectively. Results The half maximal inhibitory concentration (IC50) of tetrandrine + PTX against C6/MDR cells were (5.88 ± 0.43) nmol/L. The C6/MDR intracellular accumulation of PTX and R123 were increased by 9.4-fold and 12.3-fold in the presence of 10 μmol/L tetrandrine. Accordingly, the apoptosis rate of C6/MDR cells treated with tetrandrine + PTX was 2.3-fold higher than PTX treatment. The tetrandrine-mediated multidrug resistance reversal was involved with the downregulation of P-gp expression and the stimulation of P-gp ATPase activity. Conclusion The combination of tetrandrine and PTX had a potential of overcoming multidrug resistance on C6/MDR glioma cells in vitro.