TNP-470对小鼠肝癌生长抑制作用的研究

A study of inhibiting effect of TNP-470 on the growth of the mice bearing hepatocellular carcinoma

目的:研究血管形成抑制剂TNP-470对小鼠种植性肝癌生长抑制及其作用机制。方法:小鼠H22肝癌细胞先在KM小鼠皮下成实体瘤,再原位接种于KM小鼠肝脏。原位种植肝癌模型小鼠20只,分为两组,对照组:隔日皮下注射溶剂(3%酒精),共7次;TNP-470组:隔日皮下注射TNP-470(30mg/kg),共7次。用药两周后处死小鼠,检测原位肿瘤的长径及其垂直径(a,b),肿瘤体积按公式V=0.5×ab2计算;治疗前后小鼠体重;肿瘤组织送检ki-67、凋亡、微血管密度;另取肿瘤组织送检电镜。结果:TNP-470治疗组肿瘤生长较对照组有抑制(P<0.05),两组治疗后体重变化无明显差异;相比于对照组,TNP-470对增殖指数无明显影响(P>0.05),凋亡指数增加,微血管密度明显减少(P<0.05);电镜显示:TNP-470组可见凋亡的内皮细胞及肿瘤细胞。结论:TNP-470对小鼠原位种植瘤有生长抑制作用,TNP-470作用的靶点主要是血管内皮细胞。

twenty orthotopic transplantation of the KM mice bearing H22 hepatoeellular carcinoma were divided randomly into 2 groups： control group （3%ethanol, qod, 7 times） ;TNP-470 group （30mg,/kg, qod, 7 time）. Total mice were sacrificed two weeks after tveatment. Detect the longest and perpendicular dimension （a, b） of the tumor , the volume of the tumor was calculated according to the formula： v = 0.5 × ab^2, the pre - therapeutic and the pest - therapeutic weight of the mice;immunohistochemistry was used to detect ki -67, apeptosis, MVD;electron microscope was used to detect apeptosis. Results ： The tumor growth of TNP - 470 group was slower than the control （ P 〈 0.05）, there was no significant difference in the weight alternation of the mice between the pre - therapeutic group and the pest - therapeutic group （ P 〉 0.05 ） ; there was no significant difference in the PI between the TNP - 470 group and the control （P 〉 0.05 ）, on the contrary, in the AI and MVD （ P 〈 0.05 ） ; electron microscope indicates that apeptotic endothelial cell and tumor cell could be seen in the TNP - 470 group. Conclusion ： TNP - 470 have the anti -tumor effect,the direct target of TNP -470 is the endothelial cell, the mechanism of additive effect of TNP - 470 may be through the way of inducing the apeptosis of the endothelial cell.