端粒酶抑制剂对口腔肿瘤细胞生长的影响  

The Effect of Telomerase Inhibitors on Oral Squamous Carcinoma Cells

作　　者：杨志强[1] 陈雯[2] 张桥[2] 陈广胜[1] 雷毅雄[3] 易菲[3] 

机构地区：[1]广州医学院第二附属医院口腔科,510260 [2]广州中山医科大学公共卫生学院卫生毒理学教研室 [3]广州医学院化学致癌研究所

出　　处：《华西口腔医学杂志》2003年第3期231-234,共4页West China Journal of Stomatology

基　　金：广州医学院科研基金资助项目 (编号 30 30 0 51 1 8)

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(AS_ONS)对上述肿瘤细胞株的作用 ,用MTT试验测定细胞毒作用 ;3H_TdR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　AS_ONS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 ,AS_ONS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AS_ONS在体外有抑制端粒酶活性和抗肿瘤细胞增殖的作用 。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 \+3 H_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 G\-1 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. \;

关 键 词：端粒酶抑制剂 口腔肿瘤 细胞生长 影响 抗肿瘤药物 细胞凋亡 

分 类 号：R739.8[医药卫生—肿瘤]