rhGH联合5-FU治疗人胃癌裸小鼠皮下移植瘤的作用及机制

Inhibitory effect of rhGH combined with 5-FU on human gastric cancer transplanted in nude mice

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(rhGH2IU/(kg·d))、5-FU组(5-FU25mg/(kg·d))、联合组(rhGH2IU/(kg·d)+5-FU25mg/(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 [rh GH 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 rh GH 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.