CD147 and matrix metallo-proteinase (MMP) 2 and MMP9 expression in multidrug resistant breast cancer cells treated with P-glycoprotein substrate drugs

Abstract

To investigate effects of P-glycoprotein (gp) substrate drugs on the expression of CD147 and MMP2 and 9 in multidrug resistant breast cancer cells. MDR human breast cancer cell line, MCF7/AdrR, and its sensitive parental line, MCF7, were treated with various concentrations of P-gp substrate drugs, including paclitoxel and vincristine, and P-gp nonsubstrate drugs, bleomycin, in serum-free media. At the end of the treatment, expressions of CD147 and MMP2 and 9 were determined by real-time PCR and western blot. Increased expressions of CD147 and MMP2 and 9 were observed in multidrug resistant cancer cells compared with their parental MCF7 cells. After treatment with bleomycin, the expression of CD147 and MMP2 and 9 in both MCF7 and MCF7/AdrR cells remained unchanged (P > 0.05). However, treatment with paclitoxel and vincristine resulted in a remarkable over-expression of CD147 and MMP2 and 9 at both transcription and protein levels in MCF7/AdrR cell line (P < 0.05), while MCF7 cells failed to show similar response. P-gp substrate drugs can greatly upregulate the expression of CD147 and MMP2 and 9 in multidrug resistant breast cancer cells, therefore enhancing the tumor metastatic capability.