Fukuoka K, Saijo N
Nihon Rinsho. 1996 Jan;54(1):250-8.
We reviewed recent investigations on apoptosis related to anticancer chemotherapy. The study of programmed cell death, apoptosis, has become one of the main stream in cellular biology, particularly in immunology, developmental biology and oncology. To determine whether the apoptotic cell death induced by anticancer agents could be inhibited by bcl-2 oncogene, we established a bcl-2 transfected human small cell lung cancer cell line, SBC-3/Bcl-2. SBC-3/Bcl-2 showed higher resistance to ADM, CPT-11 and MMC compared to the parental line SBC-3. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl-2. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and Taxol between SBC-3 and SBC-3/Bcl-2 (Ohmori T, et al: Biochem Biophys Res Commun 1993). These results suggest that bcl-2 can modulate the cytotoxicity of some anticancer agents by inhibiting the process of apoptosis. We speculate that some apoptotic pathways are bcl-2-dependent and others bcl-2-independent.
我们回顾了近期有关抗癌化疗相关细胞凋亡的研究。程序性细胞死亡即细胞凋亡的研究已成为细胞生物学的主流之一，尤其是在免疫学、发育生物学和肿瘤学领域。为了确定抗癌药物诱导的细胞凋亡性死亡是否能被bcl-2癌基因抑制，我们建立了一种转染了bcl-2的人小细胞肺癌细胞系SBC-3/Bcl-2。与亲代细胞系SBC-3相比，SBC-3/Bcl-2对阿霉素（ADM）、伊立替康（CPT-11）和丝裂霉素（MMC）表现出更高的抗性。琼脂糖凝胶电泳显示，用CPT-11或MMC处理后，SBC-3出现典型的DNA片段化。相比之下，相同浓度的药物并未在SBC-3/Bcl-2中诱导DNA片段化。然而，SBC-3和SBC-3/Bcl-2对顺铂（CDDP）、依托泊苷（VP-16）、嘧啶亚硝脲（ACNU）、甲氨蝶呤（MTX）和紫杉醇（Taxol）的敏感性没有差异（大森T等人：《生物化学与生物物理研究通讯》，1993年）。这些结果表明，bcl-2可通过抑制细胞凋亡过程来调节某些抗癌药物的细胞毒性。我们推测，一些凋亡途径是bcl-2依赖性的，而其他途径则是bcl-2非依赖性的。
