The chemosensitizing potential of GF120918 is independent of the magnitude of 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 case 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 the MDR cell line for the various anti-cancer drugs tested. These data suggest that GF120918 is a potent antagonist of P-gp mediated multidrug resistance, even in the case of high levels of resistance, as was the case with paclitaxel and taxotere (2560 and 2215 fold more than the sensitive parent cell line respectively).
Myer
M S
MS
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, University of Pretoria, Pretoria 0001, South Africa.
Joone
G
G
Chasen
M R
MR
van Rensburg
C E
CE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology; D000077143:Docetaxel; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000494:pharmacology; D043823:Taxoids; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000166:Acridines; D007546:Isoquinolines; D009363:Neoplasm Proteins; D043823:Taxoids; D044005:Tetrahydroisoquinolines; D000077143:Docetaxel; D014747:Vinblastine; D005047:Etoposide; C083501:Elacridar; D017239:Paclitaxel; D000077235:Vinorelbine; D003630:Daunorubicin