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. 2025 Nov;398(11):15573-15586.
doi: 10.1007/s00210-025-04219-3. Epub 2025 May 9.

Astragaloside IV regulates macrophage polarization via the TLR4/NF-κB/STAT3 pathway to inhibit the malignant phenotype of renal clear cell carcinoma

Zhanshi Wang  1 , Chao Feng  1 , Guodong Chen  1 , Qi Cai  2
Affiliations

Astragaloside IV regulates macrophage polarization via the TLR4/NF-κB/STAT3 pathway to inhibit the malignant phenotype of renal clear cell carcinoma

Zhanshi Wang et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 Nov.

Abstract

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.

Keywords: Astragaloside IV; Macrophage polarization; Renal clear cell carcinoma; TLR4/NF-κB/STAT3.

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Conflict of interest statement

Declarations. Ethics approval: The protocol of the study was approved by the Ethics Committee of Tongde Hospital of Zhejiang Province. Consent for publication: All authors have agreed to publish this manuscript. Competing interests: The authors declare no competing interests.

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