| 苏燕燕,杨翀,张宗祥,叶宇,应佳可.瑞戈非尼通过CSF1-R信号通路调节肿瘤相关巨噬细胞增强PD-1抗体在结直肠癌中疗效的研究[1][J].浙江中西医结合杂志,2023,33(10): |
| 瑞戈非尼通过CSF1-R信号通路调节肿瘤相关巨噬细胞增强PD-1抗体在结直肠癌中疗效的研究[1] |
| Regorafenib enhances the efficacy of PD-1 antibody in colorectal cancer by regulating tumor-associated macrophages through CSF1-R signaling pathwaySu Yanyan,Yang Chong,Zhang Zongxiang, Ye Yu, Ying Jiake |
| 投稿时间：2023-02-14 修订日期：2023-08-31 |
| DOI： |
| 中文关键词: 结直肠癌 瑞戈非尼 CSF1-R信号通路 肿瘤相关巨噬细胞 |
| 英文关键词:Colorectal cancer Regorafenib CSF1-R signaling pathway Tumor-associated macrophages |
| 基金项目:浙江省医药卫生科技计划项目(2020KY221) |
|
| 摘要点击次数: 581 |
| 全文下载次数: 2 |
| 中文摘要: |
| 目的 探讨瑞戈非尼（Regorafenib，Reg）通过CSF1-R信号通路调节肿瘤相关巨噬细胞（Tumor-associated macrophages，TAMs）增强PD-1抗体（PD-1 antibody，anti-PD-1）在结直肠癌中的疗效，并分析其机制。方法 接种结肠癌细胞CT26于BALB/c小鼠，建立结直肠癌移植瘤模型，模型小鼠随机分为CT26组、CT26+Reg组、CT26+anti-PD-1组和CT26+Reg+anti-PD-1组，进行药物治疗后观察荷瘤小鼠移植瘤的生长情况。取肿瘤组织，通过Western Blot和免疫组化检测瘤内p-CSF1-R和CSF1-R表达，流式细胞术检测肿瘤单细胞悬液中TAMs并区分M1、M2表型。提取小鼠骨髓来源巨噬细胞（Bone marrow-derived macrophages，BMDMs），分别诱导成M1、M2型巨噬细胞，并用Reg处理细胞，qRT-PCR检测相关基因表达水平，Western Blot检测巨噬细胞表面CSF1-R蛋白表达。结果 相较于CT26组，药物处理后肿瘤体积和质量均显著减小，与单独使用Reg或anti-PD-1相比，Reg和anti-PD-1联合用药物使移植瘤的体积和重量进一步减小；Western Blot和免疫组化结果显示，Reg处理后，瘤内p-CSF1-R表达显著下调；流式结果显示Reg处理后，M2型巨噬细胞比例显著下降，M1型巨噬细胞比例显著增加；qRT-PCR结果也表明，Reg处理能增加BMDMs中M1表型比例并下调M2表型比例，同时Western Blot结果显示，Reg处理能显著下调M2型巨噬细胞表面p-CSF1-R蛋白的表达水平。结论 Reg通过CSF1-R信号通路调控TAMs，增强anti-PD-1在结直肠癌中的疗效。 |
| 英文摘要: |
| Abstract Objective To Investigate the effect of Regorafenib (Reg) on the enhancement of PD-1 antibody (anti-PD-1) by tumor-associated macrophages (TAMs) through CSF1-R signaling pathway. To investigate the efficacy of anti-PD-1 in colorectal cancer and its mechanism. Methods Colon cancer cells CT26 were inoculated into BALB/c mice to establish the model of transplanted tumor of colorectal cancer. The model mice were randomly divided into CT26 group, CT26 + Reg group, CT26 + anti-PD-1 group and CT26 + Reg + anti-PD-1 group. After drug treatment, the growth of transplanted tumor in tumor-bearing mice was observed. The expression of p-CSF1-R and CSF1-R in tumor tissue was detected by Western Blot and immunohistochemistry, and the expression of TAMs in tumor single cell suspension was detected by flow cytometry to distinguish M1 and M2 phenotypes. Mouse bone marrow-derived macrophages (BMDMs) were extracted and induced into M1 and M2 type macrophages, respectively. The M1 and M2 type macrophages were treated with Reg, and the expression levels of related genes were detected by qRT-PCR. The expression of CSF1-R protein on the surface of macrophages was detected by Western Blot. Results Compared with CT26 group, the tumor volume and mass were significantly reduced after drug treatment, and the volume and mass of transplanted tumors were further reduced by the combination of Reg and anti-PD-1 compared with Reg or anti-PD-1 alone; Western Blot and immunohistochemistry results showed that the expression of p-CSF1-R was significantly down-regulated after Reg treatment, and flow cytometry results showed that the proportion of M2 macrophages was significantly decreased and the proportion of M1 macrophages was significantly increased after Reg treatment; The results of qRT-PCR also showed that Reg treatment could increase the proportion of M1 phenotype and down-regulate the proportion of M2 phenotype in BMDMs, and Western Blot showed that Reg treatment could significantly down-regulate the expression level of p-CSF1-R protein on the surface of M2 macrophages. Conclusion Reg regulates TAMs through CSF1-R signaling pathway and enhances the efficacy of anti-PD-1 in colorectal cancer. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
