Astragaloside III inhibits MAPK-mediated M2 tumor-associated macrophages to suppress the progression of lung Cancer cells via Akt/mTOR signaling pathway

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-04-04 DOI:10.1016/j.intimp.2025.114546

Yan Sun , Jia-Qi Liu , Wen-Jing Chen , Wei-Feng Tang , Yao-Long Zhou , Bao-Jun Liu , Ying Wei , Jing-Cheng Dong

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引用次数: 0

Abstract

Tumor-associated macrophages (TAMs) play a key role in facilitating a range of cancerous processes by modulating the tumor microenvironment thus being a target for cancer treatment. Astragaloside III (AS-III), a compound derived from Astragalus triterpenoid saponins, has demonstrated immunomodulatory and anticancer properties, but the underlying mechanism remains unclear. Here, we demonstrated that AS-III suppressed metastasis, angiogenesis and induced apoptosis of lung cancer in vitro and in vivo by inhibiting macrophage M2 polarization and inducing M1 phenotype transformation. This was achieved through the inhibition of the MAPK signaling pathway. Furthermore, the tumor inhibitory effects of AS-III were found to be mediated by the Akt/mTOR pathway. Overall, these results highlight the role of AS-III in modifying the TAMs in TME, offering fresh perspectives on tumor immunotherapy by means of targeting macrophage.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.