文档介绍:5-氟脲嘧啶联用羟基喜树碱、r-干扰素对胃癌MGC-803细胞株的诱导凋亡和抗增殖作用
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作者:李英秀,孙东植,金仁君,张香花,陈海月
【摘要】目的通过5-氟脲嘧啶(5-Fu)、羟基喜树碱(HCPT)、r-干扰素(r-INF)联合作用和三种药单独作用对胃癌MGC-803细胞株的诱导凋亡和抗增殖作用的比较研究,为临床制定胃癌的联合用药方案提供科学的实验依据。方法用MTT比色法、原位细胞凋亡检测法(TUNEL法)及免疫细胞化学Ki-67染色法等进行研究。结果 MTT法检测结果,5-Fu在2~25μg/ml范围内,-50μg/ml范围内,r-IFN在1000~15000μ/ml范围内,各1/3单药浓度的三种药联合作用对胃癌MGC-803细胞株均有抑制生长作用,并表现出浓度依赖性关系;联合用药组与之对应的各单药组相比,其抑制率大多差异无显著性(P>),但略提高联合用药组单药的浓度(未提高到单药浓度)时,其抑制率差异均有显著性(P<)。TUNEL法检测结果,三种各单药和各1/3单药浓度的三种药联合作用均能诱导胃癌MGC-803细胞凋亡,肿瘤细胞凋亡率(APO%)随药物浓度的增高而上升,显示明显的量效关系,当药物作用48h时APO%达高峰;联合用药组与之对应的各单药组相比,其APO%大多差异有显著性(P<<)。增殖细胞核抗原Ki-67检测结果,三种各单药和各1/3单药浓度的三种药联合作用于胃癌MGC-803细胞株后,Ki-67阳性表达率随药物浓度的增高和时间的延长而减少,表现出浓度、时间依赖性关系;联合用药组与之对应的各单药组相比,Ki-
67阳性表达率大多差异有显著性(P<<)。结论 5-Fu、HCPT、r-IFN各单独作用和三种药联合作用对胃癌MGC-803细胞株均有诱导凋亡和抗增殖作用;联合用药组与之对应的各单药组相比,其诱导凋亡和抗增殖作用更明显,差异有显著性。因此,认为5-Fu联用HCPT和r-IFN是一种治疗胃癌的可行方案。
【关键词】 5-氟脲嘧啶;羟基喜树碱;r-干扰素;胃肿瘤;细胞凋亡;细胞增殖;Ki-67
【Abstract】 Objective parative study that effects on inducing apoptosis and anti-proliferation of 5-Fu﹑HCPT and r-INFjoint action and three kind of medicines alone affect on MGC-803 cell line of gastric cancer to provide the scientific experimental evidence for institute association medication plan of gastric cancer on clinical. Methods To reasarch using MTT assay,the tdt-mediated dUTP biotin end labeling(TUNEL) method and immunocytochemistry Ki-67 staining method etc. Results MTT assay showed that in extent 2~25
μg/ml of 5-Fu,~50μg/ml of HCPTand 1000~15000μ/ml of r-IFN three kinds of single medicine and each 1/3 single medicine density joint action all had the inhibition action and displayed density dependence relationship on MGC-803 cell line of gastric cancer;the inhibition rate had not different significantly() among bined group with the corresponding three kinds of medicines groups,but few elevated density bined group (not to arrived density of single medicine) the inhibition rate had different significantly a