As2O3对胃癌细胞周期及端粒酶活性的影响

目的 探讨三氧化二砷（As2O3)对SGC－7901胃癌细胞端粒酶活性及细胞周期的影响及其机制。方法 细胞凋亡、细胞周期分布及相关蛋白的表达采用流式细胞术；端粒酶活性的检测采用端粒末端重复序列扩增－ELISA法（TRAP－ELISA），端粒酶亚单位mRNA及c-myc mRNA的表达采用RT－PCR技术。结果 As2O3可明显抑制SGC-7901细胞的生长，细胞凋亡率明显增加，C0/G1期细胞减少，S和G2／M期细胞增加，Bcl-2、c-myc、PCNA蛋白表达减少，Bax蛋白表达增加，端粒酶活性明显下降；端粒酶亚单位hTR是TP1 mRNA无明显变化，hTRT mRNA表达减少，同时，c-myc mRNA的表达亦减少。结论 As2O3对SGC－7901细胞的抑制作用可能是通过二条途径实现：一个是诱导细胞凋亡，另一个是通过下调hTRT mRNA的表达来下调端粒酶活性，其机制有可能与c-myc和Bcl-2基因的减少以及Bax基因的增加有关。

Effects of arsenic trioxide on telomerase activity and cell cycle of gastric cancer cell line SGC-7901

Objective To explore the effects of arsenic trioxide(As 2O 3) on telomerase activity and cell cycle of SGC 7901 cell line. Methods Human gastric cancer cell line SGC 7901 was treated with different concentration of arsenic trioxide. Changes of apoptosis, cell cycle distribution and associated genes were analysed with flow cytometry. Telomerase activity was determined by telomeric repeat amplification protocol ELISA (TRAP ELISA). Expression of mRNA in telomerase subunits and c myc were tested by RT PCR. Results Arsenic trioxide could significantly inhibit the proliferation of SGC 7901. After treating with arsenic trioxide,the percentage of apoptosis, S and G 2/M phase cells were significantly increased, while the percentage of G 0/G 1 phase cells were significantly decreased. Expression of Bcl 2, c myc and PCNA was down regulated and expression of Bax was up regulated. Telomerase activity was descended with treatment time and concentration of arsenic trioxide. Further study indicated that telomerase subunits hTRT and c myc were down regulated, and telomerase subunits hTR and TP1 remained unchanged. Conclusion Two pathways may be involved in the process of proliferation inhibition by arsenic trioxide: one is inducing apoptosis and the other is down regulation of telomerase through decreasing expression of hTRT. The mechanism of the above two pathways may be related with decreasing expression of Bcl 2 and c myc and increasing expression of Bax.