Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines.
OBJECTIVE
To evaluate in vitro interactions of carboplatin, gemcitabine and paclitaxel in molecularly defined non-small-cell lung cancer lines.


METHODS
Three NSCLC lines, A549 (p16-,p53 wt, Rb wt), Calu-1 (p16-, p53-, Rb+) and H596 (p16 wt, p53 mut, Rb-) were utilized. Cells were exposed to carboplatin, gemcitabine and paclitaxel as individual drugs and in two- and three-drug combinations with various sequences of administration. Cytotoxicity was assessed with the MTT assay. Interactions between the drugs (additive, synergistic and antagonistic) were evaluated by median effect analysis.


RESULTS
Gemcitabine and carboplatin were synergistic in all three cell lines. In the A549 line, this synergy was most pronounced when gemcitabine preceded carboplatin. For three-drug combinations, paclitaxel was synergistic with gemcitabine and carboplatin regardless of sequence of administration.


CONCLUSIONS
In vitro modeling of gemcitabine and carboplatin as well as gemcitabine/carboplatin and paclitaxel demonstrates synergistic interaction regardless of p16, p53, or Rb status.
Edelman
M J
MJ
University of Maryland Greenebaum Cancer Center, Baltimore 21201-1595, USA. medelman@umm.edu
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H
H
Mullins
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D016161:Genes, Retinoblastoma / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine