Study of sodium orthovanadate as a reverser of multidrug resistance on lymphoblastic leukemic CEM/VLB100 cells.
The occurrence of multidrug resistance (MDR) is the major cause of failure of cancer chemotherapy. Finding a way to circumvent this problem is now a major challenge in oncology. Multidrug resistant CEM/VLB100 cells accumulate 10 times less vinblastine (VLB) after 30 min than their sensitive counterparts (CEM cells). At a non-cytotoxic concentration (1 mM) of sodium orthovanadate (OVN), uptake by CEM/VLB100 cells was increased 4 times while no effect was observed on CEM cells. The action on VLB uptake of OVN and verapamil (VPL), an usual MDR modulator, was additive. In CEM/VLB100 cells, OVN did not alter efflux. Its cellular mechanism of action could involve a transitory stimulation of VLB influx (x3). OVN uptake in CEM and CEM/VLB100 cells was not significantly different and reached saturation after 30 s (180 pmol/10(6) CEM cells and 150 pmol/10(6) CEM/VLB100 cells). This OVN uptake was concentration dependent. IC50 of VLB and doxorubicin were decreased by approximately 43 and 62% after 1 hour's exposure to OVN and 48 hours of culture. Under these conditions, OVN was more efficient than OVN.