胃泌素对人结肠癌裸鼠移植瘤的促增殖作用

Promoting effects of gastrin on transplanted human colonic carcinoma in nude mice

目的 :为探讨胃泌素对人结肠癌裸鼠移植瘤的作用及机制。方法 :建立人结肠癌SW480细胞株裸鼠移植瘤模型 ,观察在5肽胃泌素(PG)作用下移植瘤的体积和重量的变化 ;采用放射免疫法测瘤细胞内cAMP含量 ;用流式细胞术测DNA、蛋白质和细胞周期。实验动物随机分为2组 :PG组(皮下注射PG每只4μg,2/日)及对照组(皮下注射生理盐水 ,每只0.4ml,2/日) ,每组5只裸鼠 ,连续用药35d。结果 :移植瘤的体积、重量 ,瘤细胞内cAMP、DNA、蛋白质含量PG组均显著高于对照组(P<0.05 ,P<0.01) ,PG组G0/G1 期细胞数显著低于对照组(P<0.01) ,而S期、G2M期细胞数和增殖指数均显著高于对照组(P<0.05 ,P<0.01)。结论 :胃泌素在体内具有促进人结肠癌SW480细胞株分裂和增殖的作用 ,这种作用是通过增加cAMP、DNA和蛋白质的含量 ,从而促进癌细胞从G0/G1 期进入到S期和G2M期。本实验为结肠癌病人施行内分泌治疗提供了实验依据。

Objective: To study the effects of gastrin on the transplanted human colonic carcinoma in the body of nude mice. Methods: After the transplantation of human colonic carcinoma cell line SW480 into the body of nude mice, the mice of the PG group (5 mice) received hypodermical injection of pentagastrin (4 μg,bid) and those of the control group received saline injection. The changes of the size and weight of the transplanted carcinoma were measured. The cAMP content of the carcinoma cells was determined with radioimmunoassay. DNA, protein content and cell cycle were observed with flow cytometry. Results: The size and weight of the transplanted carcinoma and the content of cAMP, DNA and protein of the carcinoma cells were significantly higher in the PG group than those in the control (P<0.05,P<0.01). The number of cells in the G0/G1 phase was significantly lower in PG group than in the control (P<0.01) and the cell number and proliferation index in the S and G2M phases were markedly higher in the PG group than in the control (P<0.05,P<0.01). Conclusion: Gastrin exerts a promoting effect on the cell division and proliferation of human colonic carcinoma cell line SW480 in mice. The mechanism might be that gastrin promotes the synthesis of cAMP, DNA and protein in the carcinoma cells and then accelerates the cell growth from G0/G1 to S and G2M phase. Our findings provides theoretical basis for the hormone therapy for colorectal carcinoma.