The effect of CXCR4 inhibitor on radiosensitization of triple negative breast cancer

TANG Xinyu; CAO Yuandong; SUN Xinchen

doi:10.3969/j.issn.1009-0460.2017.11.003

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.