The effect of 5 '-(N,N-dimethyl)-amiloride on cytotoxic activity of doxorubicin and vincristine in CEM cell lines

Intracellular pH (pH(i)) plays an important role in anticancer drug accumul ation in cancer cells. Resistant cells often express membrane P-glycoprotei n responsible for active drug extrusion and participating in increased pHi. In the present paper, we report on the influence of Na+/H+-exchanger inhib itor, 5'-(N,N-dimethyl)-amiloride (AMI), on the cytotoxic effects of doxoru bicin (DOXO) and vincristine (VCR) in the parental CEM, and resistant CEM/D NR and CEM/VCR cell lines. The obtained results revealed a potentiating eff ect of AMI to both anticancer drugs in parental CEM line. However, AMI did not significantly potentiate the effect of DOXO or VCR in resistant CEM cel l lines. We conclude, that inhibition of Na+/H+-exchanger by AMI is not suf ficient for reversal of drug resistance in the tested CEM/DNR and CEM/VCR c ell lines and the possible change in pH(i) does not affect the mechanisms o f cell resistance.