ヒト口腔へん平上皮癌細胞株における抗癌剤によるアポトーシスの誘導

Abstract

Although the primary target sites have been identified for many anticancer agents, little is known about the mechanisms by which anticancer agents cause the selective death of cancer cells. Squamous cell carcinoma, a major cancer in the head and neck region, is often resistant to anticancer agents. To investigate the mechanisms by which anticancer agents act cytotoxically on squamous cell carcinomas arising in the head and neck region, the effects of carboplatin (CBDCA), 5 -fluorouracil (5 -FU), or both on NA cells, a cancer cell line established from a patient with squamous cell carcinoma of the tongue, were examined. Although both anticancer agents, either alone or in combination, exerted cytotoxic effects against NA cells, no additive or synergistic effect was observed. The cytotoxic effects of these agents were mediated by apoptotic DNA damage of NA cells. Evidence for this was provided by the specific pattern of internucleosomal DNA fragmentation, as detected by electrophoresis, specific ELISA, and H33258 DNA specific fluorochrome dye. These results indicate that the cytotoxic effect of CBDCA or 5 -FU might be mediated by the process known as apoptosis. Furthermore, Northern blot analysis revealed that c-myc mRNA expression was down-regulated by both anticancer agents.