Experimental Study Of The Inhibition Of The Specific CXCR4 AntagonistAMD3100 In The Colorectal Cancer Liver Metastasis

Objective:To investigate the inhibition of the specific CXCR4 antagonist AMD3100 in the colorectal carcinoma liver metastasis and explore its regulatory mechanism.To prove the significance of SDF-1/CXCR4 axis in the colorectal carcinoma liver metastasis.Methods:Culture colon carcinomas cell line Lovo,and 18 nude mice model of colorectal cancer liver metastasis was established by splenectomy technique,Then mice were randomly divided into 3 groups:Control group(saline solution) ,treatment group of low concentration AMD3100(0.1mmol/L , 0.1ml/d) and treatment group of high concentration AMD3100(0.15mmol/L, 0.1ml/d ) .The differences of liver metastasis between the groups were compared.Six weeks after implantation,the inhibition rates,the number of the livers metastasis,pathology characteristic of the liver metastasis,and microvessel density were evaluated respectively after the mice were sacrificed.Result1. There was no difference of the incidences of liver metastasis.2. The number of the livers metastasis was 21.00±3.90,13.00±1.79,2.17±1.17,the value of treatment group were also decreased(P < 0. 05),and the level of the treatment group of high concentration AMD3100 was lower than the treatment group of low concentration AMD3100(P < 0. 05).3. The diameter of the primarily tumors was 14.67±7.00mm(Control group), 5.17±0.75mm ( treatment group of low concentration AMD3100 ) and 2.83±1.33mm(treatment group of high concentration AMD3100),and the diameter of the liver metastasis was 3.42±2.24mm,2.26±1.12mm and1.54±0.78mm,the value of treatment group were decreased,and the level of the treatment group of high concentration AMD3100 was lower than the treatment group of low concentration AMD3100.4. The microvessel density of primarily tumors and the livers metastasis were 34.00±3.90,17.83±4.36,7.33±2.07and 33.33±3.83,19.67±4.03,6.83±4.36,the value of treatment group were also decreased(P < 0. 05),and the level of the treatment group of the high concentration AMD3100 was lower than the treatment group of low concentration AMD3100(P < 0. 05).Conclusion1. The specific CXCR4 antagonist AMD3100 greatly affects the development of colorectal cancer liver metastasis. It can inhibit in the colorectal carcinoma liver metastasis and it is more effectively of the high concentration than the low concentration in the experiment.2. The availability of AMD3100 prove the significance of SDF-1/CXCR4 axis in the colorectal carcinoma liver metastasis,SDF-1/CXCR4 is an important anti-tumor target .3. AMD3100 maybe affects the development of colorectal cancer liver metastasis by decreasing the angiopoiesis.4. SDF - 1/CXCR4 axis was one agent of the control mechanism, because AMD3100 could not suppress liver metastasis of the colorectal cancer completely.It regulate the process of the colorectal carcinoma liver metastasis with other agents.