[Characterization of the mechanism of cross-resistance to vinca alkaloids and taxoids in the human J82 bladder tumor cell line].

A phenotype of resistance to the new vinca alkaloid Navelbine was induced in the J82 human bladder carcinoma cells. The resistance factor of the resistant cell line (J82-NVB) to Navelbine was 17. The resistance phenotype of these cells is not a multidrug-resistance (MDR) phenotype. J82-NVB cells lack overexpression of P-glycoprotein and cross-resistance to MDR drugs like doxorubicin, epipodophyllotoxins or colchicine. Navelbine efflux was similar in sensitive and resistant cells, and resistance could not be explained by a difference of drug accumulation in these two cell lines. The cells were cross-resistant to vinca alkaloids and taxoids whose targets are microtubules. Immunofluorescence study of microtubules showed that depolymerization occured for the same Navelbine concentration in sensitive and resistant cells. This concentration induced growth inhibition in sensitive but not in resistant cells. Moreover, depolymerization induced by Navelbine treatment was reversible, after drug removal, in resistant cells only. This study suggests that J82-NVB cell resistance mechanism involves alterations of microtubule dynamics, allowing recovery of microtubules functions after treatment.