Linomide对人胃癌裸鼠原位种植模型生长及转移的影响

Effects of Linomide on growth and metastasis of human gastric cancer in nude mice

研究血管生成抑制剂Linomide对裸鼠种植性人胃癌生长和转移的影响。方法完整肿瘤组织块裸鼠胃壁原位种植建立类似于临床的胃癌转移模型。不同剂量Linomide经饮水给药,10周后处死动物,观察肿瘤大小及肝转移情况,并检测肿瘤内微血管数量(MVC)。结果不同剂量组的肿瘤大小有明显差别(对照组为1.36±0.81cm^3,80和160mg/kg组分别为0.84±0.51cm^3及0.62±0.35cm^3,P<0.05,0.01)。Linomide的抗转移作用呈剂量依赖形式,Linomide 80mg/kg组肝转移发生率为4/10,160mg/kg组转移发生率仅1/10,而对照组则为23/28(P<0.05,0.01)。此外,不同Linomide处理组肿瘤内微血管数量较对照组减少33%～42%(P<0.01)。结论Linomide对胃癌的体内生长和转移有较强的抑制作用。

Objective To elucidate the effect of angiogenesis inhibitor, Linomide, on the tumor growth and metastasis in nude mice implanted with human gastric cancer. Methods Patient-like metastatic model of gastric cancer was established by orthotopie implantation of intact tumor tissue into gastric wall of nude mice. Linomide (0, 80 and 160 mg/kg body weight) was given p. o. every day after implantation. The mice were sacrificed later 10 weeks, and the tumor size and tumor metastasis were detected. The microvessel counts were investigated by immunohistochemical staining with a monoclonal antibody against F-Ⅷ Rag. Results There was a significant difference in the size of the implanted tumors (control group, 1.36±0.81cm^3 versus Linomide treated group, 0.84±0.51cma and 0.62±0.35cm^3, P<0.05 and 0.01, respectively). An antimetastatic effect of Linomide was clearly demonstrated in a dose-dependent manner. In the mice given 80 mg/kg Linomide, liver metastasis developed in 4 of 10 cases. In the 160 mg/kg group, metastasis developed in only 1 of 10 mice, while metastasis developed in 19 of 28 mice of the control group (P<0.05 and 0.01, respectively). The number of metastatic loci was also significantly less in the treated group. Furthermore, the microvessel counts in tumors of treated mice was reduced to 33%～42% of that in controls (P<0.01). Conclusion Linomide has a strong inhibitory activity against in vivo tumor growth and metastasis of gastric cancer.