CYPIBI expression is induced by docetaxel: effect on cell viability and drug resistance

The cytochrome P450 CYPIBI is consistently overexpressed in tumour cells as compared to their normal counterparts, but its precise role in drug resistance is yet to be defined. It has been reported that transfection of CYPIBI results in increased resistance to docetaxel in V79 cells (McFadyen et al, 2001). In this study, we analysed changes in expression of CYPIBI mRNA associated with pulse selection of MCF-7 cells with docetaxel. Docetaxel-selected MCF-7 cells (MCF-7 Txt), which showed increased resistance to this drug as compared to parental MCF-7 cells, showed a noteworthy increase in CYPIBI mRNA expression, paralleled by increased ethoxyresorufin-O-deethylase (EROD) activity levels. This effect was not observed in cisplatin- or adriamycin-selected MCF-7 cells, or in docetaxel- selected colon, lung or pancreatic carcinoma cells. Short- term treatment with docetaxel induced CYPIBI mRNA expression in MDA 453 and BT- 20 breast carcinoma cells, but not in MCF-7 cells. Transfection of MCF-7 Txt cells with CYPIBI siRNA did not significantly affect docetaxel-induced toxicity, but it decreased cell survival in the absence of drug. Preincubation of docetaxel with recombinant CYPIBI did not affect drug toxicity in A549 cells. These results suggest that CYPIBI does not directly inactivate docetaxel, but rather might promote cell survival in MCF-7 Txt cells, providing an explanation for its association with drug resistance.