13-Methyl-palmatrubine shows an anti-tumor role in non-small cell lung cancer via shifting M2 to M1 polarization of tumor macrophages

• Published in: International immunopharmacology Vol. 104; p. 108468
• Main Authors: Wu, Zhihui, Zhou, Juan, Chen, Fangwei, Yu, Jing, Li, Hui, Li, Qingfeng, Li, Wencan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2022; Elsevier BV
• Subjects: 1-Phosphatidylinositol 3-kinase; 13-Methyl-Palmatrubine; AKT protein; Angiogenesis; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Berberine Alkaloids - pharmacology; Berberine Alkaloids - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - metabolism; Cell culture; Cell Line; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell viability; Coculture Techniques; Cytokines - genetics; Endothelial cells; Epithelial-Mesenchymal Transition - drug effects; Gelatinase B; Humans; Immunofluorescence; Interleukin 13; Interleukin 4; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Macrophage; Macrophages; Mesenchyme; Mice; Mice, Inbred BALB C; Mice, Nude; Non-small cell lung cancer; Non-small cell lung carcinoma; Polarization; Reverse transcription; Small cell lung carcinoma; Stat3 protein; Tumor-Associated Macrophages - drug effects; Tumor-Associated Macrophages - immunology; Tumors; Umbilical vein; Vascular endothelial growth factor; 13-Methyl-Palmatrubine; Polarization; Angiogenesis; Non-small cell lung cancer; Macrophage
• DOI: 10.1016/j.intimp.2021.108468
• ISSN: 1567-5769

•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.