内皮抑素对胃癌抑制作用的实验研究

Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by angiogenesis inhibitor endostatin

目的 研究内皮抑素对胃癌生长和转移的抑制作用 ,并探讨其对胃癌细胞凋亡的影响。方法 建立人胃腺癌裸鼠原位种植转移模型。将 72只荷瘤裸鼠随机分成 4组 ,对照组 3 6只 ,治疗各组每组 12只。种植后第 1周开始皮下注射内皮抑素 ,隔天 1次 ,剂量为 0mg/kg(对照组 )、2 5mg/kg、10 0mg/kg、2 0 0mg/kg(治疗组 ) ,共用 7周。种植后第 8周处死动物 ,测量原位肿瘤体积、抑瘤率、肿瘤微血管密度 (MVD)、肿瘤细胞凋亡指数 (AI) ,观察肿瘤细胞腹膜、肝、其他脏器转移及腹水情况。结果 内皮抑素剂量为 0mg/kg、2 5mg/kg、10 0mg/kg、2 0 0mg/kg时 ,原位肿瘤体积分别为 ( 15 83±5 76)mm3、( 5 91± 3 84 )mm3、( 65 7± 4 3 1)mm3、( 1 89± 1 0 2 )mm3;抑瘤率分别为 0、62 7%、95 8%、99 9% ;MVD分别为 ( 13 70± 3 90 )、( 5 73± 2 3 6)、( 2 17± 1 2 8)、( 0 66± 0 2 5 ) ;AI分别为 ( 3 91±2 5 8) %、( 6 76± 5 0 3 ) %、( 18 92± 6 75 ) %、( 2 8 5 7± 10 3 4 ) % ;腹膜转移率分别为 87 1%、5 4 5 %、16 7%、0 ;肝转移率分别为 83 9%、2 7 3 %、8 3 %、0。治疗组与对照组相比 ,组间胃癌生长和转移的抑制作用差异有显著性意义 (t=3 1 77,P <0 0 5 ) ,且抑制作用与内皮抑素?

Objective To study the effects of angiogenesis inhibitor endostatin 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. Endostatin was administered sc at dose of 0 mg/kg, 2 5 mg/kg, 10 0 mg/kg and 20 0 mg/kg every other day for seven weeks.Eight weeks after implantation, tumor size, inhibition rate, intratumoral microvessel density (MVD), apoptotic index (AI), and the presence of metastasis were evaluated respectively after the mice were sacrificed.Results Compared with the untreated controls, growth of the orthotopically implanted tumor was significantly reduced in size in mice treated with endostatin with an inhibition of rate 0,62 7%, 95 8% and 99 9% at the dosage of 0 mg/kg,2 5 mg/kg, 10 0 mg/kg, and 20 0 mg/kg, respectively The MVD was also decreased significantly in the treated mice [(13 70±3 90) versus (5 73±2 36), (2 17±1 28) and (0 66±0 25)]. The AI was increased significantly in the treated mice [(3 91±2 58)% versus (6 76±5 03)%, (18 92 ± 6 75)% and (28 57±10 34)%]. The incidences of peritoneal metastases was also significantly inhibited in the treated mice (87 1% versus 54 5%, 16 7% and 0). The incidences of liver metastases was also significantly inhibited in the treated mice (83 9% versus 27 3%, 8 3% and 0). The growth and metastasis of human gastric cancer implanted in nude mice were significantly inhibited in a dose dependent manner ( P <0 05).Conclusions Angiogenesis inhibitor endostatin can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has strong inhibitory effect both on tumor growth and metastasis of human gastric cancer implanted in nude mice.