3TSR治疗裸鼠胃癌的实验研究

目的： 探讨血管形成抑制剂3TSR对人胃癌裸鼠皮下移植瘤的抑制作用及机制。方法: 建立人胃癌裸鼠皮下种植瘤模型,实验分为对照组(腹腔注射PBS 0.2 mL)、3TSR组(腹腔注射3TSR 3 mg/kg BW)，每组8只。给药3周后处死动物,提取瘤体，测量各组荷瘤体积，HE染色检测肿瘤坏死面积百分比，免疫组织化学方法检测肿瘤微血管表达、肿瘤细胞增殖指数，原位末端标记法(TUNEL法)检测肿瘤细胞凋亡率,CD31/TUNEL/DAPI重复染色法测定肿瘤血管内皮细胞凋亡率。结果: 3TSR组平均肿瘤体积为(648.34±126.90) mm3,较对照组显著缩小(P<0.05)； 3TSR组平均肿瘤坏死面积百分比为（39.6±7.8）%,较对照组扩大69.2%，2组间有显著差异(P<0.05)。3TSR组肿瘤平均微血管数为12.8±4.1,平均微血管面积为（689.3±118.6）μm2，均显著低于对照组(P<0.05)，3TSR组增殖指数和凋亡率分别为(40.0±7.1)%和(3.4±1.2)%，与对照组比较无显著差异(P>0.05),3TSR组肿瘤血管内皮细胞凋亡率为(11.6±2.8)%,显著高于对照组的(2.9±1.5)%,P<0.05。结论: 3TSR能抑制裸鼠胃癌新生血管形成，具有显著减少肿瘤体积、肿瘤血管和增加肿瘤细胞坏死的作用，但对胃癌细胞无直接抑制作用，其机制可能与诱导内皮细胞凋亡有关。

Therapeutic effect of 3TSR on gastric carcinoma in nude mice

AIM: To investigate the anti-tumor efficacy of angiogenic inhibitor three hrombospondin-1 type repeats (3TSR) on gastric cancer. METHODS: Human gastric carcinoma cell line SGC-7901 was inoculated subcutaneously to BALB/c mice, and then the mice were divided into two groups (8 mice each): control group and 3TSR group. After administration of 3TSR by intraperitoneal injection for 3 weeks, mice were sacrificed. The tumor volume and percentage of necrotic area were detected. The micro-vessel index and cell proliferation index were detected by immunohistochemistry method. The apoptosis rate of gastric carcinoma cells was measured by TUNEL method. The vascular endothelial cell apoptosis rates were detected by CD31/TUNEL/DAPI staining. RESULTS: The tumor volume in 3TSR group was (648.34±126.91)mm3, significantly lower than that in control group (P<0.05). The percentage of tumor necrosis area in 3TSR group was (39.6±7.8)%, almost increased by 69.2% than that in the control. Average micro-vessel numbers and micro-vessel area in 3TSR were 12.8±4.1 and (689.3±118.6) μm2, respectively, significantly lower than those in the control. The proliferation index and apoptosis rate in 3TSR group were (40.0±7.1)% and (3.4±1.2)%, respectively. No difference between 3TSR group and the control was observed. The endothelial cell apoptosis rate in 3TSR group was (11.6±2.8)%, significantly higher than that in control group (2.9±1.5)%. CONCLUSION: 3TSR inhibits tumor angiogenesis, remarkably reduces tumor volume, average micro-vessel and increased tumor necrosis. 3TSR shows no direct inhibitory effects on gastric cancer cells. The antiangiogenesis effects of 3TSR on gastric carcinoma may be due to the induction of apoptosis of vascular endothelia cells.