Synergistic effects of Honghua injection combined with oxaliplatin in treatment of liver metastasis from colon cancer / 医学研究生学报

ABSTRACT

Objective The liver is the main target of colon cancer metastasis, and liver metastasis is important and difficult in colon cancer therapy.This study was to investigate the synergistic effects of Honghua injection combined with oxaliplatin in treatment of liver metastasis from colon cancer. Methods Spleen-preserving method was used to establish the model of liver metastasis from colon cancer.The model mice were randomly divided into 5 groupscontrol group, oxaliplatin group, low dose ( low dose of Honghua injection combined with oxaliplatin) group, medium dose ( medium dose of Honghua injection combined with oxaliplatin) group, high dose (high dose of Honghua injection combined with oxaliplatin) group (n=10).Oxaliplatin were given twice a week at a dose of 5 mg/kg.Honghua injection was given at doses of 2.5, 1.25 and 0.625 g/kg for consecutive 14 days, and the control group received sa-line.After 14 d, all the mice were killed, and the tumor inhibiting rates and liver metastasis rates were calculated.The levels of serum vascular endothelial growth factor ( VEGF) and hepatocyte growth factor ( HGF) were measured by ELISA, and the mRNA expressions of VEGF and HGF in liver were determined by PCR. Results The inhibition rate of low, middle and high dose group achieved 63.2%, 69.2%and 71.4%respectively, which was significantly higher than that of control group (P<0.01).Compared with oxaliplatin group,middle and high dose groups showed a significant higher inhibition rate (P<0.05).Compared with control group, the liver metastasis rates in middle and high dose groups significantly decreased from 90%to 60%and 50%respectively (P<0.05).The serum VEGF and HGF levels showed significant decrease in all treatment groups([83.4 ±25.6],[81.5 ±23.7],[75.8 ±19.4],[72.7 ±20.5] pg/mL),([56.2 ±13.8],[55.4 ±15.7],[48.9 ±13.6],[42.3 ±11.8]pg/mL) compared with control group ([125.3 ±36.2], [98.4 ±26.1]pg/mL) (P<0.01).The mRNA expressions of VEGF and HGF in liver were significantly decreased in all the Hong-hua injection combined with oxaliplatin groups compared with control group ( P<0.05) .Compared with oxaliplatin group, the serum VEGF level in high dose group showed a significant reduced mRNA expression of VEGF (P<0.05). Conclusion Honghua injec-tion can significantly enhance the inhibitory effects of Oxaliplatin on liver metastasis from colon cancer, and the mechanism may con-tribute to the inhibition of VEGF expression and the prevention of angiogenesis in liver.