The chemosensitizing potential of GF120918 is independent of the magnitudeof P-glycoprotein-mediated resistance to conventional chemotherapeutic agents in a small cell lung cancer line

GF120918, at 250 ng/ml, increased the sensitivity of a P-glycoprotein (P-gp )-mediated multidrug resistant (MDR) small cell lung cancer cell line (H69/ LX4) to the P-gp substrates, paclitaxel, taxotere, vinblastine, vinorelbine , daunorubicin and etoposide to levels which were either greater (in the ca se of etoposide) or close to that of the parent cell line (H69/P). This was achieved in spite of the great variation in the levels of resistance of th e MDR cell line for the various anti-cancer drugs tested. These data sugges t that GF120918 is a potent antagonist of P-gp mediated multidrug resistanc e, even in the case of high levels of resistance, as was the case with pacl itaxel and taxotere (2560 and 2215 fold more than the sensitive parent cell line respectively).