Atractylenolide II inhibits tumor-associated macrophages (TAMs)-induced lung cancer cell metastasis. (4th March 2022)

• Record Type: Journal Article
• Authors: Zhang, Yunting; Liu, Yuxi; Wang, Jianguang; Jiang, Zongying; Zhang, Lin; Cui, Yong; Zhao, Danyu; Wang, Yanjie
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 44:Number 2(2022)
• Page Start: 227
• Page End: 237
• Publication Date: 2022-03-04
• Subjects: Atractylenolide II -- lung cancer -- tumor-associated macrophages -- M2-like polarization -- STAT6 signaling pathway; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.1080/08923973.2022.2037629
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: Objective: M2-like tumor-associated macrophages (TAMs) play a crucial role in promoting tumor proliferation, angiogenesis, and metastasis. In the current study, we investigated the relationship between macrophage polarization and the antitumor effect of Atractylenolide II (AT-II) in lung cancer cells. Materials and methods: Cell viability, migration, and invasion were determined by MTT assay, wound healing assay, and transwell assay, respectively. Flow cytometry analysis showed the percentage of CD206 + cells. Gene expression was determined by real-time PCR, western blotting, and immunofluorescence staining. Lewis lung carcinoma mouse xenograft and metastasis models were used to examine the effects of AT-II on lung cancer in vivo . Results: AT-II (2.5 and 5 µM) did not cause significant inhibition of A549 cell viability but markedly inhibited IL-4/IL-13-induced M2-like polarization, evidenced by the decreased expression of the M2 surface marker CD206, down-regulation of specific M2-marker genes (Arg-1, IL-10 and TGF-β) as well as inhibition of M2 macrophages-mediated invasion and migration of A549 cells. In addition, AT-II inhibited IL-4/IL-13-induced activation of the STAT6 signaling pathway that is vital in the M2-like polarization of macrophages. In animal models, administration of AT-II (50 mg kg −1, i.g., QD for 21 days) significantly inhibited tumor growth, reduced pulmonary metastatic nodules, and down-regulated the percentages of M2 macrophages (F4/80 + and CD206 + ) in total macrophages (F4/80 + ) in tumor tissues and pulmonary metastatic nodules. Conclusions: AT-II effectively inhibits M2-like polarization, thereby inhibiting lung cancer cell metastasis both in vivo and in vitro, revealing a novel potential strategy for the antitumor effect of AT-II.