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MS-275联合低剂量顺铂对小鼠肝癌移植瘤生长抑制作用的研究

Research on Inhibitory Effect of MS-275 Combined with Cisplatin in Treatment of Mice Bearing Transplanted Hepatocarcinoma
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摘要 目的:探讨MS-275与顺铂联合应用对小鼠H22肝癌移植瘤的抑制作用及其机制。方法:将接种H22细胞的荷瘤小鼠随机分为对照组、MS-275组、顺铂组、顺铂+MS-275联合治疗组;15d后处死小鼠,通过称量各小鼠H22移植瘤的质量,计算抑瘤率;电镜观察荷瘤小鼠肿瘤组织超微结构改变;应用免疫组化(SP法)检测半胱氨酸蛋白酶3(Caspase-3)和血管内皮生长因子(VEGF)表达及微血管密度(MVD)。结果:联合治疗组对移植瘤抑制力最强,抑瘤率达66.8%,电镜下可见较为典型的细胞凋亡形态学改变;MS-Z75与顺铂联合治疗组可上调Caspase表达,下调VEGF表达并减低MVD,其与对照组比较均具有统计学差异(P<0.05)。结论:MS-275与顺铂联合应用,能明显抑制小鼠肝癌移植瘤生长,这种作用可能与诱导肝癌细胞凋亡及抑制癌内新血管生成有关。 Objective:To investigate the inhibition of cisplatin combined with MS-275 on the growth of transplanted H22 hepatocarcinoma in mice and its regulatory mechanism. Methods:The mice inoculated with H22 cells were divided into 4 groups at random: control group, MS-275 group, cisplatin group and combination group (cisplatin plus MS-275). Fifteen days later, the mice were killed, then the weight of H22 xenograft tumor was measured and the tumor-inhibiting rate was calculated. Transmission electron microscopy (TEM) was used to observe the ultramicro-structure alterations of H22 xenograft tumor tissue in BALB/c mice. The expression of Caspase, VEGF and the microvascular density were detected by immunohistochemisty (SP method). Results:The inhibitory activity was the most strong in combination group, with the inhibition rate reaching 66.8%. TEM demonstrated the existence of apoptotic cells and apoptotic bodies in H22 xenograft tumor tissue in combination group. Caspase-3 was significantly up-regulated, whereas VEGF and MVD were down-regulated in combined group (MS-275 plus DDP) compared to control group, MS-275 group and DDP group(P<0.05).Conclusion:The combination of cisplatin and MS-275 exerts a strong inhibitory effect on the growth of transplanted H22 hepatocarcinoma in mice. The effect may be related to the inducement of cellular apoptosis and the inhibition of the vascularization of transplanted hepatocarcinoma in mice.
机构地区 长江大学医学院
出处 《长江大学学报(自然科学版)》 CAS 2011年第1期137-139,0+5,共3页 Journal of Yangtze University(Natural Science Edition)
基金 湖北省教育厅科研资助项目(Q20091207) 国家大学生创新性实验计划项目(091048930)
关键词 肝癌移植瘤 MS-275 顺铂 生长抑制 Transplanted H22 hepatocarcinoma MS-275 Cisplatin Growth inhibitory
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参考文献10

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