目的 探究比卡鲁胺对乳腺癌细胞凋亡周期、巨噬细胞极化及p38/p-STAT1水平的影响。方法 CCK-8检测不同浓度（25、50、100 μmol/L）比卡鲁胺对乳腺癌细胞和巨噬细胞增殖能力的影响。将细胞随机分为RAW264.7细胞组、RAW264.7细胞＋比卡鲁胺100 μmol/L组、MCF-7细胞组、RAW264.7细胞＋MCF-1细胞组、RAW264.7细胞＋MCF-1细胞＋比卡鲁胺100 μmol/L组。流式细胞仪检测极化指标CD86和CD206表达；ELISA法检测细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）水平；Transwell检测细胞侵袭能力；流式细胞仪检测细胞周期；蛋白质印迹检测细胞中p-p38、p21、p-STAT蛋白表达。结果 卡鲁胺可抑制乳腺癌MCF-7细胞和巨噬细胞RAW264.7细胞增殖能力，且呈剂量相关性（P＜0.05）。与RAW264.7细胞组相比，RAW264.7细胞＋比卡鲁胺100 μmol/L组CD86阳性表达、IL-6和TNF-α水平显著升高，CD206阳性表达和IL-10水平显著降低（P＜0.05）。与MCF-7细胞组相比，MCF-7细胞＋RAW264.7组细胞侵袭能力、S期细胞所占比例及细胞中CDK4蛋白表达明显升高，G₀/G₁期细胞所占比例及细胞中p-p38、p-STAT1、p21蛋白表达降低（P＜0.05）。与MCF-7细胞＋RAW264.7细胞组相比，MCF-7细胞＋RAW264.7细胞＋比卡鲁胺100 μmol/L组细胞侵袭能力、S期细胞所占比例及细胞中CDK4蛋白表达明显降低，G₀/G₁期细胞所占比例及细胞中p-p38、p-STAT1、p21蛋白表达升高（P＜0.05）。结论 比卡鲁胺可通过调控乳腺癌巨噬细胞极化抑制乳腺癌细胞增殖和侵袭，阻滞细胞周期进程，其机制可能和激活p38/p-STAT1信号通路有关。

Objective To investigate the effects of bicalutamide on the apoptotic cycle, macrophage polarization and p38/p-STAT1 levels in breast cancer cells. Methods The effects of different concentrations (25, 50, 100 μmol/L) of bicalutamide on the proliferation of breast cancer cells and macrophages were detected by CCK-8. The cells were randomly divided into RAW264.7 cell group, RAW264.7 cell + bicalutamide 100 μmol/L group, MCF-7 cell group, RAW264.7 cell + MCF-1 cell group, RAW264.7 cell + MCF-1 cell + bicalutamide 100 μmol/L group. Expressions of CD86 and CD206 were detected by flow cytometry. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were detected by ELISA. Transwell was used to detect cell invasion ability. The cell cycle was measured by flow cytometry. The expression of p-p38, p21 and p-STAT proteins was detected by Western blotting. Results Bicalutamide inhibited the proliferation of breast cancer MCF-7 cells and macrophage RAW264.7 cells, and there was a correlation (P < 0.05). Compared with RAW264.7 cell group, CD86 positive expression, IL-6 and TNF-α levels were significantly increased in RAW264.7 cell + bicalutamide 100 μmol/L group, while CD206 positive expression and IL-10 levels were significantly decreased (P < 0.05). Compared with MCF-7 cell group, invasion ability, S phase cells, and CDK4 protein expression were significantly increased in MCF-7 cell + RAW264.7 group, while the proportion of G₀/G₁ phase cells and p-p38, p-STAT1 and p21 protein expression were decreased (P < 0.05). Compared with MCF-7 cells + RAW264.7 cells group, the invasion ability, the proportion of S phase cells and the expression of CDK4 protein in MCF-7 cells + RAW264.7 + bicalutamide 100 μmol/L group were significantly decreased. The proportion of G₀/G₁ phase cells and the protein expression of p-p38, p-STAT1 and p21 in cells were increased (P < 0.05). Conclusion Bicalutamide can inhibit breast cancer cell proliferation and invasion by regulating breast cancer macrophage polarization and blocking cell cycle progression by a mechanism that may be related to activation of p38/p-STAT1 signaling pathway.

R966；R979.1

吴阶平医学基金会临床科研专项资助基金项目（320.6750.2021-10-54）