过表达von Hippel-Lindau蛋白抑制小鼠结肠癌的生长及肝转移的研究

Overexpression of von Hippel-Lindau protein inhibits the growth of colon cancer and liver metastasis in mice

目的本研究拟探索在体内和体外过表达VHL蛋白能否抑制结肠癌的生长和转移。方法 应用含有VHL的腺病毒在体外及体内过表达VHL蛋白。在体外检测结肠癌细胞CT26的增殖、凋亡和迁移,应用Western blot检测相关蛋白的表达。建立结肠癌皮下移植瘤和肝转移癌模型并判断治疗效果。结果过表达VHL蛋白通过调控COX-2、Bcl-2和MMP-9的表达抑制结肠癌细胞CT26增殖和侵袭,促进CT26细胞凋亡。在体内过表达VHL蛋白可抑制结肠癌皮下移植瘤的增长和结肠癌的肝转移。结论 过表达VHL蛋白可抑制结肠癌的增长和转移,促进结肠癌细胞凋亡,提示VHL可能作为结肠癌治疗的一个潜在靶点。

Objective To investigate whether overexpression of VHL can inhibit the growth and metasta-sis of colon cancer .Methods Adenovirus vectors containing VHL were used to overexpress VHL protein in vitro and in vivo.The proliferation,apoptosis and migration of colon cancer cells CT 26 were examined in vitro.The ex-pressions of related proteins were detected by Western blot analysis .Subcutaneous and liver metastasis of colon cancer models were established and the therapeutic effects were evaluated .Results Overexpression of VHL pro-tein inhibited the proliferation and invasion of CT26,and promoted the apoptosis of CT26 via the regulation of COX-2,Bcl-2 and MMP-9.Overexpression of VHL protein inhibited the growth of subcutaneous colon cancer and liver metastasis in vivo .Conclusion Overexpression of VHL protien can inhibit the growth and metastasis of colon cancer ,and enhance the apoptosis of colon cancer ,indicating that VHL can be used as a potential target for colon cancer therapy .