羟基喜树碱诱导胃癌细胞凋亡的实验研究  

Apoptosis in gastric cancer cells induced by hydroxycamptothecine

作　　者：江石湖[1] 涂水平[1] 谭继宏[1] 蒋晓华[1] 乔敏敏[1] 章永平[1] 吴云林[1] 

机构地区：[1]上海第二医科大学瑞金医院

出　　处：《中华消化杂志》1999年第1期19-21,共3页Chinese Journal of Digestion

基　　金：上海市科委科学技术发展基金

摘　　要：目的研究羟基喜树碱（ＨＣＰＴ）诱导胃癌细胞的凋亡作用，探讨其治疗胃癌的作用机制。方法应用ＭＴＴ、ＴＵＮＥＬ染色、流式细胞仪技术研究ＨＣＰＴ对胃癌细胞ＳＧＣ－７９０１、ＭＫＮ－４５、ＭＫＮ－２８的细胞毒和诱导凋亡的作用。结果ＨＣＰＴ具有很强的细胞毒作用，对三株不同分化程度胃癌细胞的ＳＧＣ－７９０１（中分化）、ＭＫＮ－４５（低分化）、ＭＫＮ－２８（６高分化）的ＩＣ５０为０．００８～０．０１２ｍｇ／ｍｌ。ＨＣＰＴ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”。流式细胞仪计数显示，ＨＣＰＴ诱导胃癌细胞ＳＧＣ－７９０１、ＭＫＮ－４５、ＭＫＮ－２８的凋亡率分别为２１．８８％、１２．３５％、３０．２６％。ＨＣＰＴ诱导胃癌细胞的凋亡率与胃癌的分化程度有关。ＴＤＴ染色法显示，细胞凋亡指数在１２．３５％～３０．２６％之间。ＨＣＰＴ的作用表现为细胞周期特异性，ＨＣＰＴ主要作用于细胞周期的Ｓ期，抑制细胞增殖和诱导细胞凋亡，使细胞阻滞于Ｓ期。结论ＨＣＰＴ对胃癌细胞具有很强的细胞毒作用，诱导凋?Objective To study the mechanism of actions of hydroxycamptothecine(HCPT) on inhibiting human gastric cancer cells.Methods Morphologic changes, cytotoxicity rate, apoptosis of gastric cancer cells (SGC-7901、MKN-45、MKN-28) were studied by light microscopy, MTT assay, TUNEL method and flow cytometry after treatment with HCPT. Results The results showed HCPT had a remarkable cytotoxic effect on gastric cancer cells. The IC50 of HCPT to SGC-7901,MKN-45,MKN-28 were 0.01mg/ml, 0.012 mg/ml,0.009mg/ml,respectively. After 12 hours of exposure to HCPT, gastric cancer cells presented some morphologic features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Some typical subdiploid peaks before G0/G1 phase were observed. The apoptotic rates of SGC-7901, MKN-45,MKN-28 were 21.88%, 12.35%, 30.26%, respectively. HCPT showed a remarkable cell cycle specificity in inducing death and apoptosis in G1 phase, blocking the S phase.Conclusion HCPT can inhibit human gastric cancer cells and induce apoptosis. The induction of apoptosis would be a very important mechanism of HCPT in the treatment of gastric cancer.

关 键 词：胃癌细胞 羟基喜树碱 细胞凋亡 细胞毒 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]