STUDY OF SODIUM ORTHOVANADATE AS A REVERSER OF MULTIDRUG-RESISTANCE ON LYMPHOBLASTIC LEUKEMIC CEM VLB(100) CELLS/

The occurrence of multidrug resistance (MDR) is the major cause off fa ilure of cancer chemotherapy. Finding a way to circumvent this problem is now a major challenge in oncology. Multidrug resistant CEM/VLB(100 ) cells accumulate 10 times less vinblastine (VLB) after 30 min than t heir sensitive counterparts (GEM cells). At a non-cytotoxic concentrat ion (1 mM) of sodium orthovanadate (OVN), uptake by CEM/VLB(100) 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 modulato r, was additive. In CEM/VLB(100) 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/VLB(100) cells was not sig nificantly different and reached saturation after 30 s (180 pmol/10(6) CEM cells and 150 pmol/10(6) CEM/VLB(100) 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.