Abstract: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, P<0.05). 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, P>0.05), 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 (P>0.05), but improved the weight loss of the mice (P<0.05) 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.