三氧化二砷和顺铂对大肠癌细胞端粒酶活性及细胞凋亡的影响(英文)

目的探讨三氧化二砷（As2O3）和顺铂（DDP）对人大肠癌细胞株CCL-187端粒酶活性及细胞凋亡的影响。方法大肠癌细胞株CCL-187与空白培养液，含1．0μmol／L As2O3、0．2μg／mL,DDP、1．0μmol／L As2O3，合用0．2μg/ml DDP的培养液共同孵育1～6d。MTT法计算细胞生长抑制率，电镜下观察细胞形态学变化，RT-PCR法检测细胞端粒酶hTERT-mRNA的表达，TRAP-PCR-ELISA法检测细胞端粒酶活性。结果1．0μmol／L As2O3能促进细胞分化，0．2μg/mL DDP和合用组均能诱导细胞凋亡，同时都下调端粒酶hTERT-mRNA的表达，降低端粒酶的活性，且具有时间依赖性。用药组与对照组相比差异有极显著性（P〈0．01）；合用组与单药组相比差异有极显著性（P〈0．01）。细胞生长抑制率与细胞端粒酶hTERT-mRNA的表达、端粒酶活性的下调呈负相关。细胞端粒酶hTERT-mRNA的表达与细胞端粒酶活性呈正相关。结论1．0μmol／LAs2O3对人大肠癌CCL-187细胞有促进分化的作用，0．2μg／mL DDP和合用组有诱导凋亡的作用，其机制可能是下调细胞端粒酶hTERT-mRNA的基因表达，从而抑制端粒酶的活性。

Effects of Arsenic Trioxide and Cisplatin on telomerase activity and apoptosis of human colon cancer cell line

Objective] To explore the effects of Arsemic Trioxide (As2O3) and Cisplatin (DDP) on telomerase ac-tivity and apoptosis of human colon cancer cell line CCL-187. Methods] CCL-187 and CCL-187 with 1.0 μmol/L As2O3, 0.2 μg/mL DDP, 1.0 μmol/L As2O3 combining with 0.2 μg/mL DDP were cultured for one to six days. The cell growth restrain rate was defected by MTr assay. The cell morphologic changes were observed under electron micro- scope. The expression of hTERT at mRNA levels was analyzed by RT-PCR. Telomerase activity was determined by TRAP-PCR-ELISA. Results] Cell was induced differentiation by 1.0 μmol/L As2O3 ,but apoptesis by 0.2μg/mL DDP and 1.0 μmol/L As2O3 combining with 0.2 μg/mL DDP, at the same time, the telomerase activity was reduced and the hTERT-mRNA expression was downregulated in a time-dependent manner. They were very significantly different from negative control's (P<0.01). As2O3 combining with DDP was very significantly different from the corre- sponding individual drug groups (P<0.01). The cellular restrain rate was in dose negative con'elation with the down-regulation of hTERT-mRNA, the reduction of telomerase activity. The reduction of telomerase activity was closely correlated with the down-regulation of the hTERT-mRNA. Conclusions] 1.0 μmol/L As2O3 can induce differentia- tion, 0.2μg/mL DDP, 1.0μmol/L As2O3 combining with 0.2 μg/mL DDP can induce apoptosis of CCL-187. Its mecha- nism is perhaps reducing the telomerase activity through the down-regulation of the hTERT-mRNA expression.