guanosine-diphosphate and Carcinoma--Adenosquamous

Since taxol (NSC 125975) and tiazofurin (NSC 286193) attack at two different sites in microtubular synthetic processes, we tested the rationale that the two drugs might be synergistic in human ovarian (OVCAR-5), pancreatic (PANC-1) and lung carcinoma (H-125) cells and in rat hepatoma 3924A cells. In human OVCAR-5, PANC-1, H-125 and rat 3924A cells, for taxol the anti-proliferative IC50 was 0.05, 0.06, 0.03 and 0.04 microM, respectively; for tiazofurin IC50 = 8.3, 2.3, 1.8 and 6.9 microM. Thus, the concentrations for taxol required for IC50 for inhibiting cell proliferation were 166-, 38-, 60- and 173-fold lower than those for tiazofurin. Taxol and tiazofurin proved synergistic in all four cell lines tested. The synergism of taxol with tiazofurin should have implications in the clinical treatment of human solid tumors with particular relevance to ovarian, pancreatic, lung and hepatocellular carcinomas.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Carcinoma; Carcinoma, Adenosquamous; Cell Division; Drug Screening Assays, Antitumor; Drug Synergism; Female; Guanosine Diphosphate; Guanosine Triphosphate; Humans; Liver Neoplasms, Experimental; Lung Neoplasms; Ovarian Neoplasms; Paclitaxel; Pancreatic Neoplasms; Rats; Ribavirin; Spindle Apparatus; Tumor Cells, Cultured