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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 (siRNA) targeting human growth hormone receptor (hGHR) combined with 5-FU on hepatic metastasis of human colon cancer cells. Methods The liver metastasis model of human colon cancer cell line SW480 BALB / c was established and siRNA interference plasmids were constructed according to the hGHR gene target. The tumor-bearing mice were randomly divided into 6 different treatment groups: saline group, plasmid group, 5-FU + plasmid group and 5-FU + plasmid + GH group. The liver metastasis of each group was observed. Results The number of hepatic metastases in each group was significantly lower than that in normal saline and GH group (2.67 ± 1.37 vs.10.17 ± 1.94,10.50 ± 1.38, P <0.05) -FU combined with liver metastases slightly lower than the two alone (2.33 ± 1.03 vs.3.17 ± 0.98,2.67 ± 1.37), but the difference was not statistically significant (P> 0.05); in the basis of 5-FU + plasmid Addition of GH did not increase the incidence of liver metastases (P> 0.05), but decreased the body weight of mice induced by GHR inhibition and chemotherapeutic drugs (P <0.05). CONCLUSIONS: siRNA targeted inhibition of hGHR can reduce the occurrence of hepatic metastasis in SW480 human colon cancer cells. GHR may play an important role in tumor metastasis.