夫马吉欣联合氟尿嘧啶抗人胃癌细胞生长机制探讨

目的：探讨夫马吉欣（TNP-470）联合氟尿嘧啶对人胃癌细胞株SGC-7901裸鼠皮下移植瘤的抗肿瘤机制。方法：建立人胃癌裸鼠皮下移植瘤模型,随机分为对照组：5%葡萄糖液0.2mL/只;TNP-470组：0.6mg（0.2mL）/只;5-FU组：1.2mg（0.2mL）/只;联合用药组：5-FU：1.2mg（0.2mL）/只＋TNP-470：0.6mg（0.2ml）/只,腋窝皮下注射,隔日1次,连续用药24d。每4d测量肿瘤大小,停药后24h处死裸鼠,称取肿瘤质量,计算抑瘤率,免疫组化检测移植瘤组织中血管内皮生长因子（VEGF）、环氧化酶-2（COX-2）、微血管密度（MVD）及凋亡指数。结果：治疗后TNP-470组、5-FU组、联合用药组肿瘤的体积、质量均低于对照组（P〈0.05）;5-FU组瘤质量、体积低于单用TNP-470组（P〈0.01）,联合用药组、肿瘤质量体积和质量最低（P〈0.01）。TNP-470组、5-FU组和联合用药组的抑瘤率分别为22.29%、69.52%和86.46%。TNP-470组胃癌组织中VEGF、COX-2、MVD较对照组明显降低,凋亡指数升高（P〈0.05）,TNP-470联合5-FU组的VEGF、COX-2、MVD较其他3组都有降低,凋亡指数较其他3组升高（P〈0.05）。结论：TNP-470能通过抑制VEGF、COX-2、MVD的表达抑制肿瘤新生血管形成,诱发肿瘤细胞凋亡,抑制肿瘤生长,TNP-470联合5-FU抗胃癌生长作用更强。

Study on the Mechanism of TNP-470 Combined with Fluorouracil Inhibiting of Gastric Cancer

Objective：To investigate the effect of TNP-470 combined with Fluorouracil inhibiting of gastric cancer cell line SGC-7901 transplanted on BALB/C-nu/nu nude mice.Methods： Cultured cells were divided into 4 groups： the control group（5%GS 0.2ml each mouse）,TNP-470 group（0.6mg in 0.2ml 5% GS to each mouse）,5-FU group（1.2mg in 0.2ml 5%GS to each mouse） and the combined group（5-FU 1.2mg and TNP-470： 0.6mg in 0.2ml 5%GS to each mouse）.All were axillary subcutaneously injected every two days till 24 days.The tumor size was measured every four days,then mice were killed in 24 hours after treatment for weighing.Vascular endothelial growth factor（VEGF）,cyclooxygenase-2（COX-2）,micro-vessel density（MVD） and apoptosis index alteration in tumor tissue were detected respectively.Results： The groups of using TNP-470,5-FU and TNP-470 combined 5-FU therapy had less tumor volume and weight than that of control group（P0.05）.5-FU group had less tumor volume and weight than that of TNP-470 group（P0.01）,and the combined group had the least tumor volume and weight（P0.01）.The tumor inhibition rate of TNP-470,5-FU and combined therapy groups were 22.29%,69.52% and 86.48%,respectively.The protein of COX-2 and VEGF,The amount of MVD was lower and the apoptosis index was higher in TNP-470 group than that of the control group（P0.05）.The protein of COX-2 and VEGF,The amount of MVD was lower and the apoptosis index was higher in the combined therapy group than that of the other three groups（P0.05）.Conclusions： TNP-470 can inhibit the growth of gastric cancer.The mechanisms of inhibiting may be associated with down regulation of COX-2,VEGF expression and MVD amounts to increase tumor poptosis.TNP-470 combined with 5-FU shows more marked inhibition on the growth of gastric cancer.