rhGH联合5-FU治疗人胃癌裸小鼠皮下移植瘤的作用及机制

摘要

目的 探讨重组人生长激素(rhGH)联合氟尿嘧啶(5-FU)治疗人胃癌裸小鼠皮下移植瘤的效果及作用机制.方法 选取成功建模的人胃癌MKN-45裸鼠皮下移植瘤模型小鼠72只,采用随机数字表法分为空白组(等量生理盐水处理)、GH组(rhGH 2 IU/(kg·d))、5-FU组(5-FU 25 mg/(kg·d))、联合组(rhGH 2 IU/(kg·d)+5-FU25 mg/(kg·d)),每组18只,对比各组小鼠的体质量、荷瘤体积、抑瘤率、肿瘤细胞周期占比、肿瘤组织中Caspase-8、Caspase-9蛋白的表达,观察小鼠的血生化指标.结果 5-FU组、联合组小鼠荷瘤体积、荷瘤质量、S期细胞占比显著的低于空白组和GH组(P＜0.05),抑瘤率、肿瘤细胞G0期/G1期、G2期/M期占比、Caspase-8、Caspase-9蛋白表达水平显著的高于空白组和GH组(P＜0.05);5-FU组与联合组小鼠荷瘤体积、荷瘤质量及抑瘤率、肿瘤细胞G0期/G1期、G2期/M期、S期占比、Caspase-8、Caspase-9蛋白表达水平比较,差异无统计学意义(P＞ 0.05);5-FU组的白蛋白、总蛋白、白细胞、红细胞、血小板水平均低于空白组、GH组及联合组(P＜0.05),谷丙转氨酶水平高于空白组、GH组及联合组(P＜0.05);联合组白细胞水平较空白组和GH组降低(P＜0.05).结论 rhGH联合5-FU治疗人胃癌裸小鼠皮下移植瘤不影响5-FU的抗癌效果,同时可以改善5-FU引起的体质量减低及相关化疗毒副作用.%Objective To investigate the effect of recombinant human growth hormone (rhGH) in combination with fluorouracil (5-FU) on human gastric cancer subcutaneously transplanted in nude mice and its mechanism.Methods 72 MKN-45 tumor model nude mice were randomly divided into blank group (equal volume saline),GH group [rhGH 2 IU/(kg·d)],5-FU group [5-FU 25 mg/(kg·d)],and combination group [rhGH 2 IU/(kg·d) + 5-FU 25 mg/(kg·d)],The expression of Caspase-8 and Caspase-9 in tumor tissues were observed,and the blood biochemical indexes of the mice were measured.Results Tumor volume and mass,as well as S phase cell proportion in the 5-FU group was significantly lower than that in the control group and GH group (P ＜ 0.05),while the inhibition rate of tumor cells,and Caspase-8 and Caspase-9 expression levels were higher in the 5-FU group than that in the control group and GH group (P ＜ 0.05).No significant difference was seen between 5-FU group and combination group with regard to the tumor volume,tumor mass,the inhibition rate,cell cycle changes,as well as Caspase-8 and Caspase-9 protein expression (P ＞ 0.05).In the 5-FU group,the level of albumin,total proteins,and blood cells were lower,while alanine aminotransferase level was higher,than that in the control group,GH group and combination group (P ＜ 0.05).In combination group,level of white blood cells was decreased compared with that in the control group and GH group (P ＜ 0.05).Conclusion rhGH in combination with 5-FU does not affect the anti-cancer effect of 5-FU in the treatment of human gastric cancer in nude mice,but can improve the side-effect caused by 5-FU with regard to the blood parameters.