Triptolide reverses MCF-7/ADR cell resistance by down-regulating P-glycoprotein expression

Objective: To explore the reversal effects of triptolide (TP) on drug-resistance of adriamycin (Adriacin doxorubicin, ADR)-resistant human breast cancer cell lines (MCF-7/ADR) in vivo and in vitro. Methods: effects of triptolide and adriamycin on MCF-7 and MCF-7/ADR cell proliferation was measured by CCK-8, the reversal effect of triptolide on the drug-resistance of MCF-7/ADR cells was also measured by CCK-8; flow cytometer for testing the effect of triptolide and adriamycin on cell apoptosis was detected by flow cytometer; the expression level of Pglycoprotein was determined by Western blotting. Results: Different concentrations of adriamycin and triptolide at had inhibitory effects on the viability of MCF-7 and MCF-7/ADR cells respectively, with a concentration-dependent manner. To be specific, IC50 values of adriamycin on MCF-7 and MCF-7/ADR cells were 110.6±2.6 and 806.9±4.6 μg/ml, respectively, with an resistance index of 7.29. The IC50 values of triptolide on MCF-7 and MCF-7/ADR cells were 330.5±3.5 and 345.2±2.8 nmol/L, respectively, with a resistance index of 1.04. A combination of triptolide at non-toxic dosage levels with adriamycin reversed the drug resistance of MCF-7/ADR, with a reversal fold up to 3.65±0.21, induced cell apoptosis of MCF-7 and MCF-7/ADR, and could also significantly inhibit the growth of subcutaneous MCF-7/ADR tumor, as well as down-regulated the expression of P-glycoprotein in tumor cells in vitro and in vivo. Conclusions: Triptolide can significantly reverse the resistance of MCF-7/ADR cells, and P-glycoprotein is involved in regulating the drug-resistant effects of MCF-7/ADR cells.