13-Methyl-palmatrubine shows an anti-tumor role in non-small cell lung cancer via shifting M2 to M1 polarization of tumor macrophages.
Int Immunopharmacol
; 104: 108468, 2022 Mar.
Article
en En
| MEDLINE
| ID: mdl-35066343
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSION:
13MP suppresses TAM-mediated NSCLC progression via transforming the polarization of TAM from M2 to M1.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Plantas_medicinales
Asunto principal:
Alcaloides de Berberina
/
Carcinoma de Pulmón de Células no Pequeñas
/
Neoplasias Pulmonares
/
Antineoplásicos
Idioma:
En
Revista:
Int Immunopharmacol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China