重组人内皮抑素联合应用5氟脲嘧啶对胃癌裸鼠移植瘤的影响

The effect of recombinant human endostatin combined with 5-Fluorouracil on the growth of xenografted gastric cancer in nude mouse

目的探讨重组人内皮抑素(recombinanthumanendostatin, rhES)与5氟脲嘧啶(5 fluorouracil, 5 FU)联合应用对胃癌裸鼠移植瘤生长的抑制作用。方法建立胃癌异位移植BALB/C裸鼠模型,分为4组,每组6只。分别注射生理盐水,腹腔内注射5 FU(10mg/kg),rhES组瘤周注射rhES(2mg/kg)同时给予5 FU与rhES,每天1次,连用10d。计算肿瘤体积、抑瘤率及肿瘤缩小率,检测肿瘤组织血管内皮生长因子(VEGF)、碱性成纤维生长因子(bFGF)、血管内皮生长因子C(VEGF C)、Ⅷ因子相关抗原(FⅧAg)、增殖细胞核抗原(PCNA)、bcl 2表达及肿瘤细胞凋亡指数(AI)。结果rhES+5 FU组肿瘤体积为(43±2)mm3, 5 FU组为(169±45)mm3, rhES组为(95±28)mm3,对照组为(1057±114)mm3 (P<0 01 )。抑瘤率为99 6%,肿瘤缩小率为98 2%。用药前rhES+5 FU组肿瘤体积为( 207±50 )mm3,比5 FU组与rhES组下降更迅速(P<0 01 )。rhES+5 FU组与5 FU组VEGF、bFGF及VEGF C表达强度均为0 ^+;rhES+5 FU组PCNA及bcl 2表达最弱;rhES+5 FU组AI为11 7±1 1, 5 FU组为6 2±0 6,rhES组为5 8±0 8,对照组为2 4±0 6(P<0 01)。微血管密度在rhES+5 FU组为8 9±2 5,rhES组为10 0±1 5,均低于5 FU组(27 3±1 7)与对照组(29 9±2 3) (P<0 01 )。结论联合应用5 FU及rhES能显著抑制胃癌?

Objective This experiment was to identify the influence of recombinant human endostatin (rhES) combined with 5-FU on the growth of a xenografted gastric cancer in nude mouse. Methods After the establishment of the model, mice were divided into 4 groups (six in each) receiving respectively, for consecutive 10 days: NS, 5-FU (10 mg/kg) intraperitoneally; rhES (2 mg/kg); and 5-FU + rhES. On 15th day tumor volume was measured. The expression of VEGF, bFGF, VEGF-C, PCNA, bcl-2 and apoptosis index (AI) were examined. The tumor inhibition rate(TIR) and tumor shrinking rate(TSR) were calculated. Results Tumor volume was (43±2) mm 3 in 5 FU+rhES group,(169±45) mm 3 in 5 FU group, (95±28) mm 3 in rhES group, (1057±114) mm 3 in control group ( P <0 01); TIR of the rhES+5 FU group was 99 6%, and TSR was 98 2% ( P <0 01). The expression of VEGF, bFGF, and VEGF C in the rhES group and rhES + 5 FU group were 0^+. The AI was (11 7±1 1) in 5 FU+rhES group,(6 2±0 6) in 5 FU group, (5 8±0 8) in rhES group, (2 4±0 6) in control group ( P <0 01). The MVD of the rhES + 5 FU group(8 9±2 5) and the rhES group(10 0±1 5) were less than 5 FU group(27 3±1 7) ( P <0 01). Conclusions rhES combined with 5 FU inhibits neoangiogenesis of gastric cancer and promotes apoptosis of a xenografted gastric cancer.