Abstract: ObjectiveTo explore the effect of Fra1 inhibitor JQ1 on TAMs phenotype and growth and metastasis of breast cancer. MethodsJQ1 toxicity to mouse macrophages (RAW 264.7) was detected by CCK8. Fra1 protein expression inhibited by JQ1 was detected by Western blot, qRT-PCR and flow cytometry were performed to check the expression of M1and M2 markers in TAMs. Transwell test was used to detect migration of 4T1 cells affected by RAW264.7. In vivo, 4T1 cells transplanted mice were used to test therapeuticeffect of JQ1 combined with Taxol. ResultsJQ1 inhibits Fra1 protein expression and M2 phenotype in RAW264.7; Fra-1 inhibition in macrophages can decrease migration of 4T1 cells. JQ1, combined with Taxol, inhibits tumor growth and lung metastasis of mouse breast cancer. ConclusionsDownregulation of Fra1in macrophages by JQ1 can suppress M2 phenotype and migration of 4T1 cells, and inhibit tumor growth and lung metastasis in mouse breast cancer model.

Key words: Fra1, small molecule inhibitor, tumor associated macrophages, breast cancer, cancer therapy