生长激素对荷瘤小鼠化疗效果影响的实验研究

目的:探讨重组人生长激素(rhGH)及其联合化疗对荷瘤小鼠的影响。方法:建立小鼠前胃癌细胞经脾接种肝转移小鼠模型,随机分为两大组。第一大组分为六组:对照组(NS组),rhGH常规剂量组(GH1组),rhGH大剂量组(GH2组),单纯化疗组(5-FU组),联合组1(常规剂量rhGH 5-FU),联合组2(大剂量rhGH 5-FU)。连续用药7 d。术后28 d将第一大组小鼠处死,观察肝转移情况,记录体重、肝重,用流式细胞仪进行DNA细胞周期分析;第二大组分组及治疗方法同前,待其自然死亡或观察满70 d后处死,记录荷瘤小鼠生存期。结果:与对照组相比较,两联合组体重增加(P<0.05),5-FU组及两联合组的小鼠肝重和肝指数均明显下降(P<0.05),生存时间延长(P<0.05);两联合组小鼠肝重和肝指数较5-FU组有所下降(P(0.05),但生存时间明显延长(P<0.05);与对照组相比,两GH组S期细胞百分比及细胞增殖指数(PI)增加(P<0.05),两联合组S期细胞百分比及PI均降低(P<0.05);与5-FU组相比较,两联合组的G2/M期细胞百分比和PI均降低(P<0.05)。两联合组之间、两GH组之间两两比较,各指标无显著性差异。结论:rhGH联合化疗可明显延长小鼠的生存期。rhGH上调增殖状态的细胞数量,增加肿瘤对化疗的敏感性,联合化疗明显降低肿瘤细胞的增殖活性,抑制肿瘤生长。

Study on the effect of growth hormone and chemotherapy in tumor bcaring micc

Objective:To study the effect of recombinant human growth hormone(rhGH) and its combination with chemotherapy(5-FU) in tumor bearing mice.Methods:Hepatic metastases model were established in 615 mice by splenic injection of proventriculus squamous carcinoma cell(MFC).Among them,sixty mice were divided randomly into 6 groups(ten per group): control(NS),GH1,GH2,flurouracil(5-FU),flurouracil plus rhGH(GH1 5-FU) and flurouracil plus rhGH(GH2 5-FU).Body weights were measured every week.On the 28~(th) day,animals in each group were executed.The weight of body and liver was measured,and cell cycle of tumor DNA was determined by flow cytometry(FCM). Other 48 animals were divided randomly into 6 groups(eight per group) and treated with the same methods as above.They were fed till death to observe survival time. Results:Body weights in the GH1 (5-FU) and the GH2 5-FU group were increased than that of control group(P<0.05).In the 5-FU,GH1 5FU and the GH2 5-FU group,liver weights and liver coefficients were significantly lower and lifespans were longer than those of control group(P<0.05).In the GH1 5-FU and the GH2 5-FU group,the liver weights and liver coefficients were lower and the lifespans were longer than those of the(5-FU) group(P<0.05).DNA cell cycle kinetics analyses showed that the percentage of S-phase and proliferation index(PI) were increased significantly in GH1 and GH2 group and were decreased significantly in GH1 5-FU and GH2 5-FU group when compared with control groups(P<0.05).The percentage of G_(2) M-phase of hepatic tumors in GH1 (5-FU) and the GH2 5-FU group was significantly decreased compared with that of 5-FU group(P<0.05).There were no differences in body weight,liver(weight,)liver coefficient and PI between the GH1 and the GH2 group,and the same results were obtained between GH1 5-FU and GH2 5-FU group.Conclusion:Flurouracil combined with rhGH can significantly inhibit tumor cells growth.rhGH can enhance tumor response to chemotherapy by increasing the percentage of proliferating tumor cells.