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| 西黄丸调控MDSCs改善乳腺癌肺转移的作用及机制研究 |
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张畅1,2, 郭姗琦1, 刘金锋3, 郝剑3,4
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1.天津中医药大学第一附属医院肿瘤科, 天津 300381;2.平煤神马医疗集团总医院中医科, 平顶山 467000;3.南开大学附属南开医院中西医结合肿瘤研究中心, 天津 300102;4.天津医科大学总医院风湿免疫科, 天津 300052
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| 摘要: |
| [目的] 探讨西黄丸对三阴性乳腺癌肺转移的机制。[方法] 构建三阴性乳腺癌4T1-BALB/c原位荷瘤小鼠，流式细胞术检测荷瘤小鼠血液、骨髓、肺组织内骨髓源性抑制细胞（MDSCs）；通过苏木精-伊红（HE）染色确定小鼠肺转移微环境形成时间；利用蛋白质印迹（Western blotting）检测肺组织相关蛋白水平；通过对比各组小鼠肺转移微环境形成时间、肺组织骨髓及外周血中MDSCs数量、肺转移结节、肺转移组织相关蛋白探究西黄丸对乳腺癌肺转移的作用及机制。[结果] 西黄丸及乳香、没药药对均在第14天对移植瘤有显著抑制作用；西黄丸能够延长乳腺癌肺转移出现时间（17 d vs.14 d），且可以显著减少乳腺癌肺转移结节灶的数量；西黄丸能够抑制4T1-BALB/c荷瘤小鼠外周血及肺组织中MDSCs数量，且显著降低肺组织中基质金属蛋白酶9（MMP9）、S100A8/A9表达量。[结论] 西黄丸可通过调控外周血及肺组织中MDSCs数量，抑制MMP9、S100A8/A9表达重塑乳腺癌肺转移微环境形成，达到抑制乳腺癌肺转移目的。研究为西黄丸临床抗肿瘤转移应用奠定基础。 |
| 关键词: 西黄丸 MDSCs 转移前微环境 三阴性乳腺癌 |
| DOI：10.11656/j.issn.1672-1519.2023.04.14 |
| 分类号:R737.9 |
| 基金项目: |
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| Effect and mechanism of Xihuang Wan regulating MDSCs to improve lung metastasis of breast cancer |
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ZHANG Chang1,2, GUO Shanqi1, LIU Jinfeng3, HAO Jian3,4
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1.Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China;2.Department of Traditional Chinese Medicine, Pingmei Shenma Medical Group General Hospital, Pingdingshan 467000, China;3.Cancer Research Center of Integrated Chinese and Western Medicine, Nankai Hospital Affiliated to Nankai University, Tianjin 300102, China;4.Rheumatology and Immunology Department, Tianjin Medical University General Hospital, Tianjin 300052, China
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| Abstract: |
| [Objective] To explored the effects of Xihuang Wan on lung metastases in triple negative breast cancer-bearing mice. [Methods] Three-negative breast cancer 4T1-BALB/c tumor-bearing mice were constructed. Myeloid-derived immunosuppressive cells (MDSCs) from blood, bone marrow and lung tissues were detected by flow cytometry. The formation time of lung metastasis microenvironment was determined by HE staining. Western blotting was used to detect lung tissue-associated protein levels. The formation time of lung metastasis microenvironment, the numbers of MDSCs, lung metastasis nodules and lung metastasis tissue-related proteins were compared to explore the effects and mechanism of Xihuang Wan on breast cancer lung metastasis. [Results] Xihuang Wan showed inhibitory effects on tumors weight from the 14th day. It can prolong the occurrence time of lung metastasis (17 d vs. 14 d), and can significantly reduce the number of breast cancer lung metastasis nodular. Xihuang Wan can inhibit the number of MDSCs in peripheral blood and lung tissues, and significantly reduce the lung tissue expression of MMP9 and S100A8/A9. [Conclusion] Xihuang Wan can inhibit the formation of lung metastasis microenvironment by regulating MDSCs of peripheral blood and lung tissue, inhibiting the level of MMP9 and S100A8/A9, which can reshape the lung metastasis microenvironment. The study laid the foundation for the clinical application of Xihuang Pills in anti-tumor metastasis. |
| Key words: Xihuang Wan MDSCs pre-transfer microenvironment triple negative breast cancer |
