CHARACTERIZATION OF A NAVELBINE-RESISTANT BLADDER-CARCINOMA CELL-LINECROSS-RESISTANT TO TAXOIDS

A bladder carcinoma cell line (582) was selected for resistance to the new vinca alkaloid navelbine. The resistance factor of the resistant subline (J82-NVB) to navelbine was 17. P-glycoprotein was not detected in the membrane of J82-NVB cells. The lack of cross-resistance to mul tidrug-resistant (MDR) drugs such as doxorubicin, epipodophyllotoxins and colchicine, the absence of increase in navelbine efflux and the fa ct that a reduced accumulation of the drug cannot account for the resi stance level confirmed that the phenotype of resistance of J82-NVB cel ls is not a classical MDR phenotype. Moreover, verapamil did not rever se the resistance of J82-NVB cells. The cells were cross-resistant to vinca alkaloids and taxoids which share the same target protein: tubul in. Analysis of microtubules using immunofluorescence showed that disa ssembly of the microtubular network occurred for the same concentratio n of navelbine in sensitive and resistant cells. However, after treatm ent with a concentration of navelbine inducing depolymerisation in bot h sensitive and resistant cells, reassembly of the microtubular networ k was observed only in resistant cells. This study suggests that the m echanism of resistance of J82-NVB cells involves recovery from the inh ibition of microtubule dynamics induced by drug treatment.