端粒酶抑制剂对口腔肿瘤细胞生长的影响

目的　探讨端粒酶抑制剂作为肿瘤治疗药物的可行性。方法　选择人口腔鳞状细胞癌KB细胞株作为靶细胞 ,观察端粒酶抑制剂 3′叠氮3′脱氧胸腺核苷 （AZT）和人端粒酶模板区的硫代反义寡核苷酸片断（ASONS）对上述肿瘤细胞株的作用 ,用MTT试验测定细胞毒作用 ;3HTdR掺入试验测定细胞增殖速度 ;用端粒重复序列扩增法 （TRAP）半定量方法测定细胞染毒前后端粒酶活性的变化 ;流式细胞仪检测细胞凋亡和细胞周期。结果　ASONS和AZT在一定剂量范围内有抑制肿瘤细胞株繁殖的作用 ,在抑制细胞生长的同时 ,端粒酶活性降低。此外 ,ASONS和AZT还有诱导细胞凋亡以及使细胞阻滞在G1 期的作用。结论　AZT和ASONS在体外有抑制端粒酶活性和抗肿瘤细胞增殖的作用 ,这种作用可能与细胞凋亡的诱导和细胞周期的阻滞有关。

The Effect of Telomerase Inhibitors on Oral Squamous Carcinoma Cells

OBJECTIVE: To study the potential anti-tumor effect of telomerase inhibitors. METHODS: Human oral squamous carcinoma cell line KB was selected as target cell. The effects of 3'-azido-3'-deoxythymidine (AZT) and human antisense phosphorothioate (AS-ONS) for telomerase template on KB cell line were investigated. The cytotoxic effect of AZT and AS-ONS on tumor cells was quantified using MTT colorimetric assay. Assay of 3H-TdR incorporation was undertaken to measure the cell proliferation. The changes of telomerase activity after treatment was detected and quantified by telomeric repeat amplification protocol (TRAP) semi-quantitative analysis. The Flow Cytometry was used to detect apoptosis and measure cell cycle. RESULTS: Both AZT and AS-ONS inhibited the growth of KB cell line in a certain range of concentrations, and meanwhile the telomerase activity was reduced after treatment. In addition, both AZT and AS-ONS can induce apoptosis and arrest G1 phase of cell cycle. CONCLUSION: The results obtained above indicated that AZT and AS-ONS could be potentially used as an anti-oral carcinoma agent or an auxiliary treatment for cancer. Those inhibitory effects might be partially due to the induction of apoptosis and the prolongation of cell cycle.