目的 探究比卡魯胺對乳腺癌細胞凋亡周期、巨噬細胞極化及p38/p-STAT1水平的影響。方法 CCK-8檢測不同濃度（25、50、100 μmol/L）比卡魯胺對乳腺癌細胞和巨噬細胞增殖能力的影響。將細胞隨機分為RAW264.7細胞組、RAW264.7細胞＋比卡魯胺100 μmol/L組、MCF-7細胞組、RAW264.7細胞＋MCF-1細胞組、RAW264.7細胞＋MCF-1細胞＋比卡魯胺100 μmol/L組。流式細胞儀檢測極化指標CD86和CD206表達；ELISA法檢測細胞因子腫瘤壞死因子-α（TNF-α）、白細胞介素-6（IL-6）、白細胞介素-10（IL-10）水平；Transwell檢測細胞侵襲能力；流式細胞儀檢測細胞周期；蛋白質(zhì)印跡檢測細胞中p-p38、p21、p-STAT蛋白表達。結(jié)果 卡魯胺可抑制乳腺癌MCF-7細胞和巨噬細胞RAW264.7細胞增殖能力，且呈劑量相關(guān)性（P＜0.05）。與RAW264.7細胞組相比，RAW264.7細胞＋比卡魯胺100 μmol/L組CD86陽性表達、IL-6和TNF-α水平顯著升高，CD206陽性表達和IL-10水平顯著降低（P＜0.05）。與MCF-7細胞組相比，MCF-7細胞＋RAW264.7組細胞侵襲能力、S期細胞所占比例及細胞中CDK4蛋白表達明顯升高，G₀/G₁期細胞所占比例及細胞中p-p38、p-STAT1、p21蛋白表達降低（P＜0.05）。與MCF-7細胞＋RAW264.7細胞組相比，MCF-7細胞＋RAW264.7細胞＋比卡魯胺100 μmol/L組細胞侵襲能力、S期細胞所占比例及細胞中CDK4蛋白表達明顯降低，G₀/G₁期細胞所占比例及細胞中p-p38、p-STAT1、p21蛋白表達升高（P＜0.05）。結(jié)論 比卡魯胺可通過調(diào)控乳腺癌巨噬細胞極化抑制乳腺癌細胞增殖和侵襲，阻滯細胞周期進程，其機制可能和激活p38/p-STAT1信號通路有關(guān)。

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

吳階平醫(yī)學基金會臨床科研專項資助基金項目（320.6750.2021-10-54）