【摘要】 目的:研究顺铂(DDP)、丝裂霉素(MMC)、多柔比星(ADM)和长春新碱(VCR)4种化疗药物对人肝癌细胞株BEL-7404、耐阿霉素肝癌细胞株BEL-7404/ADM的细胞毒作用及其对端粒酶活性影响的关系。方法:采用MTT法测定常用4种(DDP、MMC、ADM和VCR)化疗药物对人肝癌细胞株BEL-7404、BEL-7404/ADM的体外抑制作用;以TRAP-PCR-ELISA法检测化疗药物作用后两种细胞端粒酶的活性。结果:DDP、MMC、ADM、VCR对BEL-7404均敏感,各种化疗药物IC50大小比较,DDP和ADM比VCR和MMC均小;而对BEL-7404/ADM这几种化疗药物敏感性均不同程度下降,其中以ADM及VCR尤其明显,耐药倍数分别为100·0倍、60·14倍。未加药前,肝癌亲本细胞BEL-7404和耐药细胞BEL-7404/ADM端粒酶活性均表达,加入化疗药物后,亲本细胞端粒酶活性下降明显,并呈现时间-剂量关系,而对于耐药细胞,只有高浓度的化疗药物才能抑制其端粒酶活性。结论:端粒酶活性的抑制与耐药细胞对药物敏感性存在一定关系,端粒酶可作为化疗敏感的潜在标志。更多还原

【Abstract】 OBJECTIVE:To evaluate the relationship between telomerase activity and drug-sensitivity in human hepatocellular carcinoma cell lines. METHODS: The human hepatocellular carcinoma drug-sensitive cell line BEL-7404 and drug-resistance cell line BEL-7404/ADM were treated of chemotherapeutic drugs (cisplatin DDP,adriamycin ADM,mitomycin MMC,VCR respectively). MTT was used to measure the multiplier of drug resistance. Telomerase activity was detected by TRAP-PCR-ELISA. RESULTS: The drug resistance indexes of hepatocellular carcinoma cell lines BEL-7404/ADM to ADM and MMC were 100 and 60 respectively. The telomerase activity in BEL-7404 was decreasing with the increasing of DDP, ADM, VCR, MMC concentration but not so apparent in BEL-7404/ADM. Only high concentration of DDP, ADM, MMC and VCR deregulated telomerase activity of BEL-7404/ADM in a time-depending manner. CONCLUSION: Telomerase activity is related to the drug-sensitivity in hepatocellular carcinoma drug-resistance cell. Telomerase is a potential chemosensitive marker.更多还原