摘要
目的探讨FOS相关抗原-1(Fra1)特异性小分子抑制剂JQ1对肿瘤相关巨噬细胞表型以及小鼠乳腺癌生长和转移的影响。方法 CCK8检测JQ1的细胞毒性;Western blot检测RAW264.7细胞Fra1蛋白水平;RT-q PCR和流式细胞术检测JQ1处理巨噬细胞后M1/M2相关表型分子的变化;Transwell细胞迁移实验检测JQ1处理后的RAW264.7细胞对4T1乳腺癌细胞系迁移能力的影响;小鼠荷瘤实验检测JQ1联合紫杉醇对小鼠乳腺癌的治疗效果。结果 JQ1能够抑制巨噬细胞Fra1蛋白表达和向M2型极化,降低巨噬细胞促进乳腺癌细胞迁移的能力(P<0.05);JQ1联合紫杉醇治疗明显降低小鼠乳腺癌的原位生长和肺转移(P<0.05)。结论 JQ1通过抑制巨噬细胞Fra1蛋白表达来抑制巨噬细胞向M2型极化,降低肿瘤细胞迁移能力,进而减少小鼠乳腺癌肿瘤原位生长和肺转移。
Objective To explore the effect of Fral inhibitor JQ1 on TAMs phenotype, growth and metastasis of breast cancer. Methods JQ1 toxicity to mouse macrophages （ RAW 264. 7 ） was detected by CCKS. Fral protein expression inhibited by JQ1 was detected by Western blot, RT-qPCR and flow eytometry were performed to check the expression of Mland M2 markers in TAMs. Transwell test was used to detect migration of4Tl cells affected by RAW264.7. In vivo, 4T1 cells transplanted mice were used to test therapeutic effect of JQ1 combined with Taxol. Results JQ1 inhibits Fral protein expression and M2 phenotype in RAW264.7; Fral inhibition in maerophages can decrease migration of 4T1 cells. JQ1, combined with Taxol, inhibits tumor growth and lung metastasis of mouse breast cancer. Conclusions Downregulation of Fral in macrophages by JQ1 can suppress M2 phenotype and mi- gration of 4T1 cells, inhibit tumor growth and lung metastasis in mouse breast cancer model.
出处
《基础医学与临床》
CSCD
2016年第7期934-940,共7页
Basic and Clinical Medicine
基金
国家自然科学基金(81472654)
