氧化砷抑制胃癌SGC-7901细胞增殖和诱导凋亡作用

Proliferation inhibition and apoptosis induction by arsenic trioxide on gastric cancer cell SGC 7901 *

目的研究氧化砷对胃癌细胞的增殖抑制和诱导凋亡作用．方法应用细胞集落形成实验、ＭＴＴ，ＴＵＮＥＬ染色、流式细胞仪技术，研究氧化砷对胃癌细胞ＳＧＣ７９０１的增殖抑制、细胞毒和诱导凋亡的作用．结果氧化砷能显著抑制胃癌细胞ＳＧＣ７９０１的生长，５μｍｏｌ／Ｌ氧化砷抑制程度明显强于１μｍｏｌ／Ｌ（Ｐ＜００５），５μｍｏｌ／Ｌ和１μｍｏｌ／Ｌ的氧化砷作用后的细胞集落形成率分别为１２４％±３３％和６８％±２６％，明显低于对照组的２０６％±５７％（Ｐ＜００１）．氧化砷对胃癌细胞具有较强的细胞毒作用，１０μｍｏｌ／Ｌ氧化砷作用２４ｈ细胞杀伤率为２４６％，４８ｈ接近５０％．氧化砷作用于细胞后，可看到较为典型的细胞凋亡的形态学变化：细胞核固缩，染色质凝集，呈新月型紧贴于核膜周边，核碎裂，染色质片断化，凋亡小体形成等．流式细胞仪ＤＮＡ直方图上出现典型的亚二倍体“凋亡峰”．ＴＤＴ染色法显示，细胞凋亡指数为７３％～１５１％．氧化砷的细胞毒作用呈时间和剂量依赖性，且表现为细胞周期特异性，作用４８ｈ后，ＳＧＣ７９０１细胞的细胞周期变化明显，Ｇ０／Ｇ１期细胞从５４２％下降到１７７％，而Ｇ２／Ｍ期细胞则从２０?

AIM To explore the effect of arsenic trioxide (As 2O 3) in inhibition of proliferation and induction of apoptosis of gastric cancer cell SGC 7901. METHODS Morphologic changes, proliferation ability, colony forming rate of gastric cancer cell SGC 7901 treated by As 2O 3 were studied by light microscopy, growth curve and colony forming assay. The cytotoxicity of As 2O 3 on SGC 7901 was determined by MTT assay. Apoptosis and cell cycle changes of SGC 7901 induced by As 2O 3 was investigated by TUNEL method and flow cytometry. RESULTS As 2O 3 can inhibit significantly the growth of SGC 7901. Colony forming rate of SGC 7901 with 5μmol/L As 2O 3 (6 8%±2 6%) was lower than that with 1μmol/L As 2O 3 (12 4%±3 3%, P <0 01), and much lower than that of control group (20 6%±5 3%, P <0 01). As 2O 3 had a remarkable cytotoxic effect on SGC 7901. The cytotoxic rate of 10μmol/L As 2O 3 on SGC 7901 was almost 50 0% in 48 hours. After 12 hours of exposure to the drug, SGC 7901 exhibited morphologic features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. A typical subdiploid peak before G0/G1 phase was observed by flow cytometry. The apoptotic index was 7%-15% by TUNEL and FACS assay. The effect of As 2O 3 on SGC 7901 showed a remarkable cell cycle specificity, which indicates that As 2O 3 mainly acts in G2/M phase. CONCLUSION As 2O 3 can inhibit significantly proliferation of gastric cancer cell SGC 7901 and induce apoptosis and it has a potential. value in the treatment of gastric cancer, and was worth further studies.