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目的:探讨外源性生长激素(GH)对荷瘤裸鼠GH/胰岛素样生长因子(IGF)/胰岛素样生长因子结合蛋白3(IGFBP-3)轴的影响。方法:采用人结肠癌细胞株(HCT116)建立人结肠癌细胞裸鼠移植瘤模型。取48只荷瘤裸鼠随机均分为生理盐水处理组(NS组)、氟尿嘧啶处理组(FU组)、GH处理组(GH组),FU+GH处理组(FU+GH组)。每组连续给药6 d,在给药结束后24,72 h分别处死每组6只动物,取血及移植瘤标本,应用ELISA法检测血清GH,IGF-I,IGFBP-3含量和RT-PCR法检测移植瘤IGF-I,IGF-I受体(IGF-IR),IGFBP-3的mRNA表达。结果:ELISA结果显示,给药结束后24 h,GH组和FU+GH组血清GH,IGF-I,IGFBP-3含量较NS组与FU组明显升高(均P<0.05);给药结束后72 h,各组GH,IGF-I的水平无统计学差异(均P>0.05),但GH组和FU+GH组IGFBP-3水平仍高于NS组和FU组(均P<0.05)。RT-PCR结果显示,给药结束后24 h,GH,FU,FU+GH组移植瘤组织IGF-I mRNA与IGF-IR mRNA的表达较NS组明显降低,而IGFBP-3 mRNA表达明显增加;给药结束后72 h,IGF-I mRNA与IGF-IR mRNA表达各组间无差别,但GH组,FU组和FU+GH组IGFBP-3 mRNA表达量仍明显高于NS组。结论:短期应用外源性GH所致GH/IGF/IGFBP-3轴的变化对人结肠癌移植瘤生长无促进作用。
Objective: To investigate the effect of exogenous growth hormone (GH) on the growth of GH / IGF-3 / IGFBP-3 axis in nude mice. Methods: Human colon cancer cell line xenograft model was established by human colon cancer cell line (HCT116). Forty-eight nude mice bearing tumor were randomly divided into normal saline group (NS group), fluorouracil treated group (FU group), GH treated group (GH group) and FU + GH treated group (FU + GH group). The rats in each group were dosed continuously for 6 days. Six animals in each group were sacrificed at 24 and 72 h after the administration. Blood and tumor samples were collected. Serum GH, IGF-I, IGFBP-3 levels and RT- PCR was used to detect the mRNA expression of IGF-I, IGF-I receptor (IGF-IR) and IGFBP-3 in the transplanted tumor. Results: The serum levels of GH, IGF-I and IGFBP-3 in GH group and FU + GH group were significantly higher than those in NS group and FU group (all P <0.05) at 24 h after the administration; After 72 h, the levels of GH and IGF-I in each group had no significant difference (all P> 0.05), but the levels of IGFBP-3 in GH and FU + GH groups were still higher than those in NS and FU groups (all P <0.05) . The results of RT-PCR showed that the expression of IGF-I mRNA and IGF-IR mRNA in the tumor tissues of GH, FU and FU + GH group was significantly lower than that of NS group and IGFBP-3 mRNA expression was significantly increased 24 h after the administration; IGF-I mRNA and IGF-IR mRNA expression did not differ between groups at 72 h after administration, but IGFBP-3 mRNA expression in GH, FU and FU + GH groups was still significantly higher than that in NS group. Conclusion: The changes of GH / IGF / IGFBP-3 axis caused by short-term use of exogenous GH have no effect on the growth of human colon carcinoma xenografts.