Inadequately irradiated primary tumor of primary Lewis lung carcinoma (LLC-LM) in vivo is a mechanism of radiation-enhanced LLC-LM cells in pulmonary metastasis. We observed a CXCL1/GRO alpha, is a member of the CXC family of chemokines is elevated after radiation therapy. CXCL1 protein is function with to bind the G-protein coupled receptor chemokine (C-X-C motif) receptor 2 (CXCR2) to recruit neutrophils. Reparixin is an inhibitor of CXCR2, and demonstrates activity against malignant behavior of human cancer cells xenografts. The effect of Reparixin on the radiotherapy of LLC-LM primary tumor and the effects on distant metastases have not been studied. The right thighs of C57BL/6 mice (n = 40) were injected s.c. with 1 x 10(6) LLC-LM cells. Animals were randomized to one of four groups: no irradiation, 10 Gy in one fraction, Reparixin (0.1mg/kg/day, for 5days) plus 10 Gy in one fraction, or Reparixin( 0.1mg/kg/day, for 5days) only . Tumors were clinically irradiated in each treatment group. All of the mice were killed within 21 days after the completion of radiation therapy. Examination of their lungs revealed >13 (range, 13-22) surface metastases in the 10 Gy treated mice with 3 (range, 2-7) in the no irradiation mice, in Reparixin plus 10 Gy treated mice with 6(range, 4-13), in Reparixin treated mice with 2 (range, 2-6). The lung weights had increased from 0.22 g (range, 0.21-0.24 g) in the no irradiation mice to 0.43 g (range 0.37-0.61) in the 10 Gy treated mice, in Reparixin plus 10 Gy treated mice with 0.31(range, 0.26-0.41), in Reparixin treated mice with 0.23 (range, 0.2-0.25 g). In the surface metastases and lung weight, Reparixin plus irradiation treatment were statistically significant with P < 0.001 when compare with irradiation alone. Other hand, the tumor growth curve also demonstrated that the Reparixin enhanced the tumor control of irradiation of LLC-LM tumor. In this model, the use of inadequately radiation to eradicate a primary LLC-LM tumor results in the growth of previously dormant lung metastases and suggests that combining CXCR2 inhibitor with radiation therapy may enhance local tumor control and reduce distant metastases.

Citation Format: Chia-lun Chang, Yi-Hsin Liang, Szu-yuan Wu. CXCR2 inhibitor Reparixin enhances local tumor control and reduces distant metastases in mouse tumor radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-313.