Experimental Study Of The Effect Of Recombinant Human Growth Hormone And Combined With Fluorouracil On The Development Of Hepatic Metastases Of Proventriculus Squamous Cell Carcinoma In The Mice

Objective To study the effect of recombinant human growth hormone (rhGH) and combined with chemotherapy (flurouracil, 5-FU) in tumor bearing mice.Methods Hepatic metastases model were established in one hundred and eight 615 mice by splenic injection of proventriculus squamous carcinoma cell (MFC). Among them, sixty Mice are 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). From the 15th to 21th day after surgery, GH1 and GH2 group received daily i.h. rhGH 2IU /kg and 20IU /kg, respectively. 5-FU group received daily i.c.5-FU(20mg/kg), and GH1/5-FU group received daily i.h. rhGH (2IU/kg) and i.c.5-FU(20mg/kg), and the GH2/5-FU group received daily i.h rhGH (20IU/kg) and i.c.5-FU(20mg/kg) , while control group received daily i.h 0.2 milliliter and i.c. 0.5 milliliter sterile saline.Body weights are measured every week. On the 28th day , animals in each group are executed. The weight of body and liver is measured, and cell cycle of tumor DNA is determined by flow cytometry (FCM). Other 48 animals were divided randomly into 6 groups (eight per group) and treated with the same methods as that 60 mice. 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, GH1/5-FU and the GH2/5-FU group, liver weights and liver coefficients were significantly lower and lifespan 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 lifespan 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 compared to control groups(P<0.05). The percentage of G2/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 are 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.Conclusions rhGH does not stimulate tumor growth in vivo though at a high dose and has no adverse effects on tumor bearing mice. rhGH and combined with Flurouracil can significantly inhibit tumor cells growth. rhGH enhanced tumor response to chemotherapy by increasing the percentage of proliferating tumor cells.