13-Methyl-palmatrubine shows an anti-tumor role in non-small cell lung cancer via shifting M2 to M1 polarization of tumor macrophages
•13MP reduced the malignant behaviors of NSCLC cells.•13MP promoted TAM from M2 to M1 polarization.•13MP attenuated M2-TAM-mediated NSCLC progression.•13MP repressed M2-TAM-mediated angiogenesis.•13MP abated the M2-TAM-mediated the PI3K/AKT and JAK/STAT3 pathway activation. Previous studies have sub...
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Published in | International immunopharmacology Vol. 104; p. 108468 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
01.03.2022
Elsevier BV |
Subjects | |
Online Access | Get full text |
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Summary: | •13MP reduced the malignant behaviors of NSCLC cells.•13MP promoted TAM from M2 to M1 polarization.•13MP attenuated M2-TAM-mediated NSCLC progression.•13MP repressed M2-TAM-mediated angiogenesis.•13MP abated the M2-TAM-mediated the PI3K/AKT and JAK/STAT3 pathway activation.
Previous studies have substantiated that M2-activated tumor-associated macrophages (M2-TAMs) are involved in multiple malignancies. Presently, we probe the impact and related mechanisms of 13-methyl-palmatrubine (13MP), the Corydalis yanhusuo extract, on M2-TAM-mediated non-small cell lung cancer (NSCLC) development.
IL-4 and IL-13 were adopted to induce M2-TAMs. The polarization state of TAMs was evaluated by quantitative reverse transcription PCR (qRT-PCR), Western blot (WB) and cellular immunofluorescence. NSCLC cells (A549 and NCL-H1975) were co-cultured with the conditioned medium (CM) of M2-TAMs. Followed by 13MP treatment, cell viability, proliferation, invasion, epithelial-mesenchymal transition (EMT), and in-vivo growth of NSCLC cells were determined. Additionally, human umbilical vein endothelial cells (HUVECs) were co-cultured with the CM of M2-TAMs. The tube formation assay was made to test the tube formation capacity of HUVECs, and the expression of MMP3, MMP9, and VEGF was assessed by WB in the co-culture model. Mechanistically, WB was performed to validate the expression of the PI3K/AKT and JAK/STAT3 pathways in NSCLC cells (A549 and NCL-H1975) as well as in endothelial cell lines co-cultured with M2-TAMs.
13MP inhibited the proliferation, invasion, EMT, growth and enhanced apoptosis of NSCLC cells. 13MP dose-dependently boosted the polarization of TAM from M2 to M1 state. M2-TAMs enhanced the malignant behaviors of NSCLC cells, whereas 13MP hindered M2-TAM-mediated NSCLC cell proliferation and invasion. Meanwhile, 13MP weakened the M2-TAM-mediated angiogenesis. Moreover, 13MP inactivated the PI3K/AKT and JAK/STAT3 signaling in A549 cells, NCL-H1975 cells and HUVECs.
13MP suppresses TAM-mediated NSCLC progression via transforming the polarization of TAM from M2 to M1. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1567-5769 1878-1705 |
DOI: | 10.1016/j.intimp.2021.108468 |