华西口腔医学杂志

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端粒酶抑制剂对口腔肿瘤细胞生长的影响

杨志强,陈雯,张桥,陈广胜,雷毅雄,易菲   

  1. 510260 广州医学院第二附属医院口腔科(杨志强,陈广胜),广州中山医科大学公共卫生学院卫生毒理学教研室(陈雯,张桥),广州医学院化学致癌研究所(雷毅雄,易菲)
  • 收稿日期:2003-06-25 修回日期:2003-06-25 出版日期:2003-06-20 发布日期:2003-06-20
  • 基金资助:

    广州医学院科研基金资助项目 (编号 303005118)

YANG Zhiqiang*, CHEN Wen, ZHANG Qiao,et al.   

  1. *Department of Stomatology, the Second Affiliated Hospital, Guangzhou Medical College, Guangzhou 510260, China
  • Received:2003-06-25 Revised:2003-06-25 Online:2003-06-20 Published:2003-06-20

摘要:

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。

关键词: 口腔鳞状细胞癌, 端粒酶, 抗肿瘤药物, 细胞凋亡

Abstract:

Objective To study the potential antitumor effect of telomerase inhibitors.Methods Human oral squamous carcinoma cell line KB was selected as target cell. The effects of 3′azido3′deoxythymidine (AZT) and human antisense phosphorothioate (ASONS) for telomerase template on KB cell line were investigated. The cytotoxic effect of AZT and ASONS on tumor cells was quantified using MTT colorimetric assay. Assay of \+3 HTdR 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) semiquantitative analysis. The Flow Cytometry was used to detect apoptosis and measure cell cycle.Results Both AZT and ASONS 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 ASONS can induce apoptosis and arrest G\-1 phase of cell cycle.Conclusion The results obtained above indicated that AZT and ASONS could be potentially used as an antioral 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.

Key words: telomerase, oral squamous carcinoma, anti-oral carcinoma agent, apoptosis