Combination chemotherapy studies with gemcitabine and etoposide in non-small cell lung and ovarian cancer cell lines.

摘要: Abstract Gemcitabine (2′,2′-difluorodeoxycytidine, dFdC) and etoposide (4′-demethylepipodo-phyllotoxin-9-4,6-O-ethylidene-β- d -glucopyranoside, VP-16) are antineoplastic agents with clinical activity against various types of solid tumors. Because the low toxicity profile dFdC differences in mechanisms cytotoxicity, combinations both drugs were studied vitro. For this purpose, we used human ovarian cancer cell line A2780, its cis-diammine-dichloroplatinum-resistant VP-16 cross-resistant variant ADDP, two non-small lung lines, Lewis Lung (LL, murine) H322 (human). The interaction between was determined multiple drug effect analysis (fixed molar ratio) a variable ratio. In LL line, combination at constant ratio (dFdC:VP-16 = 1:4 or 1:0.125 after 4- 24-hr exposure, respectively) synergistic (combination index [CI], calculated 50% growth inhibition 0.7 0.8, respectively; CI ic 25 concentration range, additivity found cells; synergism observed A2780 ADDP cells, which least sensitive to VP-16. Schedule dependency line; when cells exposed 4 hr prior (constant ratio, total exposure 24 hr), (CI 0.5), whereas 1.6). mechanism more detail dFdCTP accumulation 1.2-fold enhanced by co-incubation VP-16, even pronounced (1.4-fold) dFdC. dCTP levels decreased alone as well compounds, may favor phosphorylation dFdC, thereby increasing accumulation. DNA strand break (DSB) formation increased for compounds together compared each compound separately, being most (38% 0% DSB alone, respectively 97% combination). potentiation might be result repair Provided right schedule is used, certainly eligible