【摘要】 目的 探讨FOXF2表达对乳腺癌肿瘤相关巨噬细胞（TAMs）极化以及乳腺癌细胞增殖和凋亡的影响和可能机制。方法 收集30例临床乳腺癌患者的肿瘤相关巨噬细胞及配对癌旁组织巨噬细胞，qRT-PCR和Western blot检测FOXF2 mRNA和蛋白表达。转染FOXF2过表达慢病毒至小鼠腹腔巨噬细胞（PMs）,ELISA检测巨噬细胞M1/M2极化指标iNOS、TNF-α、Arg-1和IL-10表达，Western blot检测Akt/mTOR信号通路相关蛋白表达变化。将MCF-7细胞与TAMs或过表达FOXF2的TAMs共培养，CCK-8和Edu染色检测细胞增殖情况，Tunel染色检测细胞凋亡情况，Western blot检测细胞凋亡相关蛋白Bax和Bcl2表达。结果 临床乳腺癌患者的TAMs中FOXF2 mRNA和蛋白表达较配对癌旁组织巨噬细胞明显降低（P<0.05）；与对照组相比，过表达FOXF2的TAMs的M1型极化标志物（iNOS、TNF-α）表达明显升高，M2型极化标志物（Arg-1、IL-10）表达明显降低（P<0.05）;Akt/mTOR信号通路相关蛋白磷酸化水平明显降低（P<0.05）;MCF-7细胞的增殖能力降低，凋亡能力升高（P<0.05）。结论 FOXF2可能通过改变乳腺癌TAMs的极化状态影响乳腺癌细胞的增殖和凋亡过程，其机制可能与FOXF2介导Akt/mTOR信号通路调节巨噬细胞极化相关。更多还原

【Abstract】 This study was performed to investigate the effect of FOXF2 expression on tumor-associated macrophages(TAMs) polarization and breast cancer cell proliferation and apoptosis. Tumor-associated macrophages and paired paracancer tissue macrophages were collected from 30 patients with breast cancer, and the mRNA and protein expression of FOXF2 were detected by qRT-PCR and Western blotting. FOXF2 overexpressing lentivirus was transfected into mouse peritoneal macrophages(PMs). M1/M2 polarization indexes, including iNOS, TNF-α,Arg-1 and IL-10, were detected by ELISA, while Akt/mTOR signaling pathway-related proteins were detected by Western blotting. After MCF-7 cells were co-cultured with TAMs or TAMs overexpressing FOXF2, the cell proliferation was detected by CCK-8 and Edu staining, the apoptosis was detected by Tunel staining, and the apoptosis-associated proteins Bax and Bcl2 were detected by Western blotting. Data showed that FOXF2 mRNA and protein expression in TAMs from breast cancer patients were significantly lower than those in paired paracancer tissue macrophages(P<0.05); Compared with control group, the expression of M1-type polarization markers iNOS and TNF-α were increased, while the M2-type polarization markers Arg-1 and IL-10 were significantly decreased in TAMs overexpressing FOXF2(P<0.05). Furthermore, FOXF2 inhibited the phosphorylation of Akt/mTOR signaling pathway-related proteins significantly(P<0.05), and suppressed the proliferation capacity of MCF-7 cells and promoted the apoptosis capacity(P<0.05). In conclusion, FOXF2 may affect the proliferation and apoptosis of breast cancer cells by changing thepolarization of breast cancer TAMs, and the mechanismmay be related to the regulation of macrophage polarization by FOXF2-mediated Akt/mTOR signaling pathway.更多还原