循环中胰岛素样生长因子-Ⅰ水平调节结肠癌的生长和转移研究

Circulating insulin-like growth factor-I regulates colon cancer growth and metastasis

目的 探讨血清中肝特异性胰岛素样生长因子 Ⅰ (IGF Ⅰ )水平在刺激小鼠结肠癌生长和转移中的作用。方法 我们实验中所用的肝脏特异性IGF Ⅰ基因缺失 (LID)小鼠 ,其循环中IGF Ⅰ水平仅为正常小鼠 (对照组小鼠 )的 2 5 %。将Colon 3 8腺癌组织块 (碎片 )植入LID和对照组小鼠的盲肠表面。总共 15 6只 5周龄的雄鼠 (其中 82只LID小鼠 ,74只对照鼠 )接受了肿瘤移植。小鼠被随机分成两组 :一组接受腹腔注射重组人IGF 1(rhIGF 1) ,每天 2次 ,共 6周 ,另一组接受生理盐水注射。结果 接受rhIGF Ⅰ注射组的LID和对照小鼠 ,血清IGF 1和IGFBP 3水平均升高。在生理盐水注射组中 ,对照鼠的盲肠肿瘤的发生率和肝脏转移率显著高于LID小鼠。和盐水注射组相比 ,腹腔注射rhIGF 1组中 ,LID和对照组小鼠均有显著的盲肠癌发生率和肝脏转移率。对照小鼠的肝脏转移结节数明显高于LID鼠。结肠癌组织VEGF的表达和血管的密度依赖于血液中IGF Ⅰ水平。结论 血液循环中IGF I水平在结肠癌发展和转移中起了重要作用。

Objective To determine the role of serum insuli-like growth factor-I (IGF-1) levels in the process of stimulating tumor growth and metastasis in a mouse model of colon cancer.Methods Colon 38-adenocarcinoma tissue fragments were attached to the surface of the cecum in control and liver-specific IGF-1-deficient (LID) mice,in which serum IGF-1 levels were 25% of that in control mice.A total of 156 male mice at 5-weeks of age (74 control mice and 82 LID mice) received tumor transplants.Mice were divided randomly into two groups:one group was injected intraperitoneally (ip) with rhIGF-1 (2 mg/kg) twice daily for 6 weeks and the other group received saline injections.Results IGF-1 treatment increased the serum levels in both control and LID mice.In the saline-injected group,the incidence of tumor growth on the cecum as well as the frequency of hepatic metastasis was significantly higher in control mice than in LID mice.Both control and LID mice treated with rhIGF-1 displayed significantly increased rates of tumor development on the cecum and metastasis to the liver,as compared to saline-injected mice.The number of metastatic nodules in the liver was significantly higher in control mice than in LID mice.The expression of VEGF as well as vessel abundance in the colon tumors was dependent on the levels of serum IGF-1.Conclusion Circulating IGF-1 levels play an important role in tumor development and metastasis.