Abstract: Objective To investigate the radiation sensitivity of chemokine 12（CXCL12） receptor CXCR4 inhibitor AMD3100 on xenograft tumor of breast cancer of MDA-MB-231 cells in nude mice and the underlying mechanism. Methods Human breast cancer xenograft model on nude mice was established successfully， and the mice were divided into 4 groups： control group， AMD3100 treatment group， radiation group and combination group （AMD3100+radiation）， 9 mice each group. The size and weight of xenograft tumor were measured， the radiosensitization enhancement ratio was calculated and the xenograft tumor growth curve was depicted. The quantitative realtime PCR （QPCR） was used to detect the expression of CXCR4 and epidermal growth factor receptor （EGFR）. Western blotting was used to detect the protein expression of CXCR4， EGFR and matrix metalloproteinases-9 （MMP-9）. Results The radiosensitization enhancement ratio was 1:45. Compared with the control group， the gene relative expression of CXCR4 and EGFR in AMD3100 treatment group， radiotherapy group and combination group was down-regulated by 60％，45％，82％ and 56％，48％，73％， and the difference was statistically significant（P＜0.05）. The result by QPCR showed that both AMD3100 and radiotherapy could inhibit the expression of CXCR4 and EGFR （P＜0.05）， while AMD3100 and radiation combination could better inhibit the expression of CXCR4 and EGFR when compared with the AMD3100 single treatment group and radiotherapy group（P＜0.05）. The result of Western blotting showed that AMD3100 or radiotherapy could inhibit the expression of CXCR4， EGFR and MMP-9， AMD3100 and radiotherapy combination inhibited the expression of the three proteins more significantly （P＜0.05）.
Conclusion AMD3100 can enhance the radiosensitivity in nude mice xenografts of breast cancer， and the mechanism involves the down-regulation of CXCR4， EGFR and MMP-9.