Taniki T, Prajda N, Monden Y, Weber G
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200, USA.
Cancer Biochem Biophys. 1993 Sep;13(4):295-302.
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.
由于紫杉醇（NSC 125975）和硫唑嘌呤（NSC 286193）作用于微管合成过程中的两个不同位点，我们验证了这两种药物在人卵巢癌细胞（OVCAR-5）、胰腺癌细胞（PANC-1）、肺癌细胞（H-125）以及大鼠肝癌3924A细胞中可能具有协同作用的理论依据。在人OVCAR-5、PANC-1、H-125细胞以及大鼠3924A细胞中，对于紫杉醇，其抑制增殖的IC50分别为0.05、0.06、0.03和0.04微摩尔；对于硫唑嘌呤，IC50 = 8.3、2.3、1.8和6.9微摩尔。因此，抑制细胞增殖所需的紫杉醇IC50浓度比硫唑嘌呤低166倍、38倍、60倍和173倍。在所有测试的四种细胞系中，紫杉醇和硫唑嘌呤均显示出协同作用。紫杉醇与硫唑嘌呤的协同作用对于人类实体瘤的临床治疗，尤其是对卵巢癌、胰腺癌、肺癌和肝细胞癌的治疗可能具有重要意义。
