Wang Zhanshi, Feng Chao, Chen Guodong, Cai Qi
Department of Urology, Tongde Hospital of Zhejiang Province, No. 234 Gucui Road, Xihu District, Hangzhou City, Zhejiang Province, 330012, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 9. doi: 10.1007/s00210-025-04219-3.
Clear cell renal cell carcinoma (ccRCC) is a common and aggressive type of kidney cancer. This study aimed to investigate the effect of astragaloside IV (AS-IV) on ccRCC. A variety of cell experimental techniques were used, inducing macrophage polarization, and detecting relevant indicators by flow cytometry, qRT-PCR, immunofluorescence, MTT, wound healing, Transwell, and western blot. A nude mouse xenograft tumor model was constructed for in vivo studies, and siRNA interference technology was used to explore the signaling pathway. The results demonstrated successful macrophage polarization, with AS-IV inhibiting M2 macrophage polarization and promoting the transition from M0 to M1 polarization. Additionally, AS-IV suppressed ccRCC cell proliferation, migration, and invasion, while reversing the malignant effects of M2 macrophages. The study further revealed that AS-IV inhibited M2 polarization through the TLR4/NF-κB/STAT3 signaling pathway. In vivo experiments showed that AS-IV inhibited the growth of ccRCC tumors. This study revealed that AS-IV influences macrophage polarization by regulating the TLR4/NF-κB/STAT3 signaling pathway, thereby inhibiting the malignant phenotype of ccRCC. This finding provides new insights and potential therapeutic strategies for the treatment of ccRCC.
透明细胞肾细胞癌（ccRCC）是一种常见且侵袭性强的肾癌类型。本研究旨在探讨黄芪甲苷IV（AS-IV）对ccRCC的影响。采用了多种细胞实验技术，诱导巨噬细胞极化，并通过流式细胞术、qRT-PCR、免疫荧光、MTT、伤口愈合实验、Transwell实验和蛋白质免疫印迹法检测相关指标。构建裸鼠异种移植瘤模型进行体内研究，并使用小干扰RNA（siRNA）干扰技术探索信号通路。结果表明巨噬细胞极化成功，AS-IV抑制M2巨噬细胞极化并促进从M0向M1极化的转变。此外，AS-IV抑制ccRCC细胞的增殖、迁移和侵袭，同时逆转M2巨噬细胞的恶性作用。研究进一步揭示，AS-IV通过TLR4/NF-κB/STAT3信号通路抑制M2极化。体内实验表明，AS-IV抑制ccRCC肿瘤的生长。本研究揭示，AS-IV通过调节TLR4/NF-κB/STAT3信号通路影响巨噬细胞极化，从而抑制ccRCC的恶性表型。这一发现为ccRCC的治疗提供了新的见解和潜在的治疗策略。
