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目的 探讨反义hTR基因转染对胃癌细胞系SGC 790 1恶性表型的逆转作用及其在肿瘤基因治疗中的价值。方法 构建包含端粒重复序列模板区的反义hTR基因真核表达载体 ,用脂质体法将其转染至胃癌细胞系SGC 790 1,比较观察反义hTR基因转染后 790 1细胞的hTRRNA表达、端粒酶活性、体外生长增殖特性和裸鼠体内致瘤能力的变化。结果 反义hTR基因转染的 790 1细胞hTRRNA表达和端粒酶活性明显降低、体外生长增殖能力降低、接触抑制恢复、细胞凋亡率增加、软琼脂集落形成能力和裸鼠体内致瘤能力完全消失。结论 反义hTR基因转染能使 790 1细胞的端粒酶活性明显下调并逆转其恶性表型 ,提示端粒酶是肿瘤治疗的较理想靶点 ,端粒酶抑制剂具有良好的临床应用前景。
Objective To investigate the reversal effect of antisense hTR gene transfection on the malignant phenotype of gastric cancer cell line SGC7901 and its value in gene therapy of cancer. Methods The antisense hTR gene eukaryotic expression vector containing the telomeric repeat template region was constructed and transfected into gastric cancer cell line SGC 790 1 by lipofectamine 2000. The hTR RNA of 7901 cells transfected with antisense hTR gene Expression, telomerase activity, growth and proliferation in vitro and in vivo tumorigenic ability of nude mice. Results The hTRRNA expression and telomerase activity of 7901 cells transfected with antisense hTR gene were significantly decreased, the ability of growth and proliferation decreased, the contact inhibition was restored, the apoptosis rate was increased, the colony formation ability of soft agar and the tumorigenic ability in nude mice were completely disappear. CONCLUSIONS: Transfection of antisense hTR gene can significantly down-regulate the telomerase activity of 7901 cells and reverse its malignant phenotype, suggesting that telomerase is an ideal target for tumor therapy. Telomerase inhibitors have a good clinical application prospect .