Pre-clinical evaluation of new antineoplastic agents in NSCLC cell lines: evidence of histological subtype-dependent cytotoxicity.
The antiproliferative effect of paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cis-platin was studied on 5 non-small cell lung cancer (NSCLC) cell lines, 3 of which were adenocarcinoma (ADK) and 2 squamous cell carcinoma (SCC). Cellular chemosensitivity was determined using the MTT in vitro assay after 48, 72 and 96 h of exposure to drug in concentration ranging from 0.001 to 100 microM. A concentration-dependent cell growth inhibition was observed for paclitaxel, gemcitabine, topotecan, SN-38 and cis-platin in all cell lines tested. Docetaxel showed a concentration-independent cytotoxicity and was 104 times more potent than cis-platin (IC50 = 0. 001 vs. 10 microM). Paclitaxel, gemcitabine, topotecan and SN-38 were 102 times more potent than cis-platin, with median IC50 = 0.1 microM at 72 h. The level of drug-induced cell growth inhibition appeared to be correlated, for some of the six drugs tested, with the tumor histological subtype. In particular, topotecan and cis-platin were more active in squamous cell carcinoma than in adenocarcinoma cell lines (p=0.006 and 0.001 respectively at 0.1 microM concentration), while paclitaxel was more active in ADK than in SCC cell lines (p=0.004 at 0.01 microM concentration). Ca-Lu-6, a cell line that, contrary to most other lung cancer cell lines, is wild-type for most oncogenes/tumor suppressor genes, was by far the most sensitive cell line used (p=0.002, 0.003, 0.01 for paclitaxel, topotecan and cis-platin respectively, at 1 microM concentration), showing a >50% growth inhibition to new drugs at a concentration of 0.01 microM. In conclusion, all these new compounds tested were found to be more potent than cis-platin in affecting cellular proliferation of six NSCLC cell lines studied. We suggest that the specific histological subtype and molecular pattern of the cell line being treated could affect the antiproliferative effect of these drugs.
Loprevite
M
M
Department of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy.
Favoni
R E
RE
de Cupis
A
A
Pirani
P
P
Merlo
F
F
Grossi
F
F
Ardizzoni
A
A
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000494:pharmacology; D012680:Sensitivity and Specificity; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D003841:Deoxycytidine; D000077143:Docetaxel; D000077146:Irinotecan; D019772:Topotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin; D000093542:Gemcitabine