TGIF反义寡核苷酸对胃癌细胞增生和凋亡的影响

Effects of TGIF antisense oligonucleotide on proliferation and apoptosis of gastric carcinoma cells

目的:TGIF(TG interacting factor)是TGF-β和视黄醛信号传导通路的抑制分子,且MAPK通路的活化能延长其半衰期,但他在肿瘤发生中的作用尚不清楚,本研究旨在探讨TGIF反义寡核苷酸对胃癌细胞增生和凋亡的影响. 方法:将TGIF反义寡核酸瞬时转染胃癌细胞株SGC-7901, RT-PCR检测转染效率,MTT法检测胃癌细胞的增生速度, 流式细胞术分析转染细胞的细胞周期和凋亡率的变化. 结果:SGC-7901细胞转染TGIF反义寡核苷酸后,细胞增生受到部分抑制,72h后,他的抑制率达20.4%,但细胞的凋亡和细胞周期分布无明显改变.TGF-β1处理后,与突变寡核苷酸转染组细胞和未转染组细胞相比,TGIF反义寡核苷酸转染的SGC-7901细胞的增生受到明显抑制(30%),Gl 期细胞含量增加更明显. 结论:TGIF能抑制TGF-β1对细胞生长和细胞周期的负调控作用,多数肿瘤细胞和间质细胞能分泌TGF-β1,这些肿瘤细胞有可能利用TGIF甚至少量TGIF,抑制TGF-β对自身的生长抑制作用,从而促进肿瘤的发生、发展与转移.

AIM: TG interacting factor ( TGIF ) can inhibit both TGF-β and retinoid signaling pathways, moreover, the activation of MAPK pathway can lengthen its half life. However, its role in carcinogenesis is still unclear. Thus we attempt to investigate the effect of TGIF antisense oligodeoxynucleo-tide (ASDON) on proliferation and apoptosis of gastric carcinoma cells. METHODS: After gastric carcinoma cells, SGC-7901, were transfected with TGIF ASDON, we analyzed the transfect efficiency by RT-PCR, its proliferation by MTT method, cell cycle and apoptosis rate via flow cytometer. RESULTS: After transfection with TGIF ASDON, the proliferation of SGC-7901 cells was partially inhibited, and its inhibitory rate was increased to 20.4% at 72h, whereas it had no effect on cell cycle and apoptosis of SGC-7901 cells. Followed by the treatment of TGF-β1, the growth rate of cells transfected with TGIF ASDON was distinctly reduced by 30%, and the content of G1 phase cells increased more obviously compared with the cells transfected with mutated oligonucleotides or untransfected cells. CONCLUSION: TGIF can resist the negative regulation of TGF-β1 over proliferation and cell cycle. Most of tumor cells and interstitial cells can secrete TGF-β1, and tumor cells may resist the TGF-β1 mediated growth inhibition via TGIF, leading to the progression and even metastasis of tumor.