端粒酶反义寡核苷酸对MCF-7细胞端粒酶活性及细胞生长的影响

为探讨端粒酶反义寡核苷酸对人乳腺癌MCF-7细胞端粒酶活性及细胞生长的影响,应用与人端粒酶RNA组分(hTR)模板区互补的硫代反义寡核苷酸处理MCF-7细胞.发现经反义hTR寡核苷酸作用后,细胞端粒酶活性明显受到抑制,至作用后72 h,端粒酶活性较对照组降低61.0%(P<0.05);细胞生长明显受到抑制;细胞周期发生显著变化,G0/G1期细胞数增多,S期及G2/M期细胞数则减少;细胞增殖指数由0.46降低至0.29;并可观察到凋亡细胞的出现,凋亡发生率为10.7%;而无义寡核苷酸处理组及空白对照组以上各指标均无明显变化.提示端粒酶反义寡核苷酸可明显抑制乳腺癌细胞端粒酶活性,抑制细胞生长和增殖,诱导细胞凋亡;表明应用反义技术抑制端粒酶活性治疗乳腺癌可能具有广阔的前景.

Effect of Tel omerase Antisense Oligodeoxynucleotides on Telomerase Activity and Cell Growth in MCF-7 Cell Line

In order to investigate the effects of telomerase antisense oligodeoxynucleotides (ODNs) on telomerase activity and the growth of breast cancer cells, MCF-7 cells were treated with antisense phosphorothoate oligodeoxynucleotides complementary to the template region of human telomerse RNA (hTR). The results showed that telomerase activity were suppressed significantly, and decreased by 61 0 % after 72 h as compared with control group (P<0 05); The growth of MCF-7cells were inhibited significantly; Cell cycle phases were altered significantly: S phase and G 2 /M phase cells were decreased and G 0 /G 1 phase cells were increased, the proliferation index decreased from 0 46 to 0 29; Apoptosis cells were observed after 120 h, and apoptosis rate was 10 7 %. However, in the groups of nosense ODNs and control the above parameters were not changed significantly (P>0 05). The results suggest that telomerse antisense oligodeoxynucleotides can significantly suppress the telomerse activity, inhibit cell growth and cell proliferation, and induce cell apoptosis of MCF-7 cells. It may be possible to control breast cancer by inhibiting telomerse activity through antisense technique.