生长激素受体靶向siRNA联合5-FU对人结肠癌肝转移的影响  

Effect of combination of siRNA targeting growth hormone receptor and 5-fluorouracil on liver metastasis of colon cancer

作　　者：周东[1,2] 张毅[2] 粱道明[2] 袁勇[2] 李思齐[2] 曾德妙[1] 陈嘉勇[2] 

机构地区：[1]昆明医学院,云南昆明650101 [2]昆明医学院第二附属医院急诊科,云南昆明650101

出　　处：《中国普通外科杂志》2011年第7期731-735,共5页China Journal of General Surgery

摘　　要：目的探讨小分子干扰RNA(siRNA)靶向抑制人生长激素受体(hGHR)联合5-FU对人结肠癌细胞肝转移的影响。方法建立人结肠癌细胞SW480 BALB/c小鼠肝转移模型,并针对hGHR基因靶点构建siRNA干扰质粒,将荷瘤小鼠随机分成6个不同处理组,分别为生理盐水组、质粒组、生长激素(GH)组、5-氟尿嘧啶(5-FU)组、5-FU+质粒组、5-FU+质粒+GH组,观察各组肿瘤的肝转移情况。结果各组小鼠均有肝转移瘤形成,质粒组肝转移瘤数较生理盐水及GH组明显减少(2.67±1.37 vs.10.17±1.94,10.50±1.38)(P<0.05);干扰质粒与5-FU联用后肝转移瘤数略低于两者单独使用(2.33±1.03 vs.3.17±0.98,2.67±1.37),但差异无统计学意义(P>0.05);在5-FU+质粒的基础上加用GH并不增加肝转移瘤的发生(P>0.05),但能改善小鼠由GHR抑制和化疗药物的毒性引起的体质量降低(P<0.05)。结论 siRNA靶向抑制hGHR可降低小鼠中人结肠癌细胞SW480肝转移的发生,GHR在肿瘤转移中可能起了重要作用。Objective To investigate the effects of small interfering RNA targeting human growth hormone receptor（hGHR） combined with 5-fluorouracil（5-FU） on liver metastasis of colon cancer.Methods Animal model of liver metastases with human colon cancer cell SW480 was established on BALB/c mouse and siRNA interfering plasmid targeting hGHR gene was constructed.The tumor-bearing mice were randomly divided into 6 groups that included saline control group,plasmid group,growth hormone（GH） group,5-FU group,5-FU＋plasmid group and 5-FU＋plasmid＋GH group.The liver metastasis in each group was observed.Results Liver metastases were found in all the mice.siRNA interfering plasmid treatment significantly reduced the incidence of liver metastases compared with saline or GH group（2.67±1.37 vs.10.17±1.94,10.50±1.38,P0.05）.The combined treatment of interfering plasmid and 5-FU slightly decreased the incidence of liver metastases compared with plasmid alone or 5-FU alone treatment（2.33±1.03 vs.3.17±0.98,2.67±1.37,P0.05）,but had no statistical significance.On the basis of the combination of interfering plasmid and 5-FU,the additional GH did not increase the incidence of liver metastases（P0.05）,but improved the weight loss of the mice（P0.05） induced by inhibition of GHR and toxicity of 5-FU.Conclusions siRNA targeting hGHR can reduce the incidence of liver metastases of human colon cancer cell SW480 in mice.GHR may play an important role in tumor metastasis.

关 键 词：结肠肿瘤 肝转移 BALB/C小鼠 小分子干扰RNA 

分 类 号：R735.3[医药卫生—肿瘤]