封闭端粒酶活性对肺癌细胞系的生长抑制作用

GROWTH INHIBITION OF LUNG CANCER CELL LINE in vitro BY TELOMERASE ANTI-SENSE OLIGONUCLEATIDES

目的 研究端粒酶反义核苷酸对肺癌细胞体内外生长的影响 ,探讨封闭端粒酶抑制肺癌细胞生长的可行性。 方法 端粒酶反义DNA与端粒酶阳性肺癌细胞系共同培养 ,观察其对肺癌细胞端粒酶活性、细胞形态和生长特性的影响 ;荷瘤小鼠肿瘤局部注射反义DNA ,初步观察其对动物体内肿瘤有无生长抑制作用。 结果端粒酶反义DNA对两个端粒酶阳性肺癌细胞系生长、集落形成有明显的抑制作用 ,细胞形态发生明显改变。注射反义DNA裸鼠肿瘤 ,瘤重明显低于生理盐水组 (P <0 0 5 )。 结论 端粒酶反义DNA序列对肺癌细胞系有明显的生长抑制作用。

Objective To study the inhibition of lung cancer cell line by telomerase anti\|sense DNA,and discuss the possibility of using it in clinical treatment. Methods A phosphorothioate oligonucleotide(PS\|ODN) with sequence identical to the repeat sequence of the mammalian telomere 5′\|d(TTAGGG)\|3′ and a control scrambled sequence 5′\|d(TGTGAG)\|3′ were incubated with a lung cancer cell line.The effects of PS\|ODN on cell line growth,colony\|forming and growth shape were detected.The in vivo efficacy of this PS\|ODN was evaluated in a 801\|D nude mouse model.Once tumors were established these animals were administered PS\|ODN or saline for 15 days. Results Telomease anti\|sense DNA inhibit telomerase activation of cell line 801\|D growth and colony\|forming.The activity of the 6\|mer telomere mimic demonstrated a dose dependency.No activity was observed with the scrambled controls.A significant decrease in tumor weight was observed in animals given PS\|ODN, but not followig saline\|treated animale.Conclusion\ These results demonstrated that short hexameric oligonucleotide telomere exerts the growth inhibitory effect on lung cancer cell in vitro and in vivo, and suggest the potential utility of telomerase anti\|sense DNA as cancer cell inhibitors.\;[