血管生成抑制剂TNP-470对胃癌生长及转移抑制作用的实验研究

Experimental study of the effect of angiogenesis inhibitor TNP 470 on the growth and metastasis of gastric cancer in vivo

目的研究血管生成抑制剂ＴＮＰ－４７０对胃癌生长及转移的抑制作用。方法完整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。移植后第１周开始皮下注射ＴＮＰ－４７０，隔天１次，剂量为０ｍｇ／ｋｇ、１５ｍｇ／ｋｇ、３０ｍｇ／ｋｇ、６０ｍｇ／ｋｇ，共用８周。移植后第１０周处死动物，测量肿瘤大小，观察转移情况，以兔抗人Ⅷ因子抗体免疫组化染色检测肿瘤微血管密度。结果ＴＮＰ－４７０对体内胃癌的生长及转移均有抑制作用，ＴＮＰ－４７０剂量为１５ｍｇ／ｋｇ、３０ｍｇ／ｋｇ、６０ｍｇ／ｋｇ的抑瘤率分别为５９．９％、７７．０％和８４．９％，肝转移抑制率分别为５１．３％、８７．８％和８７．８％，腹膜转移抑制率分别为３２．８％、６６．４％和７７．６％。用ＴＮＰ－４７０治疗后，肿瘤的微血管密度明显减少。结论ＴＮＰ－４７０对体内胃癌的生长及转移均有抑制作用。

Objective To study the effect of angiogenesis inhibitor TNP 470 on the growth and metastasis of gastric cancer in vivo. Methods Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. TNP 470 was administered sc at doses of 0 mg/kg,15 mg/kg,30 mg/kg,60 mg/kg every other day for eight weeks. Ten weeks after implantation, the mice were sacrificed and the tumor size measured and the presence of metastasis recorded. The microvascular density was examined by immunohistochemical staining with anti human factor Ⅷ antibody. Results Compared to the untreated controls, growth of the orthotopically implanted tumor was significantly reduced in size in mice treated with TNP 470 with an inhibition rate of 59.9%, 77.0% and 84.9% at the dosage of 15 mg/kg, 30 mg/kg and 60 mg/kg, respectively. Tumor metastasis to the liver and peritoneaum was also significantly inhibited in a dose dependent manner. The microvascular density was also decreased significantly in the treated mice. Conclusion Angiogenesis inhibitor TNP 470 has strong inhibitory effect both on tumor growth and metastasis of human gastric cancer in nude mice.