(−)-Guaiol inhibit epithelial-mesenchymal transition in lung cancer via suppressing M2 macrophages mediated STAT3 signaling pathway
Yajuan Cao,
Yonghui Wu,
Hongbin Tu,
Zhan Gu,
Fengzhi Yu,
Weiling Huang,
Liping Shen,
Lixin Wang,
Yan Li
Affiliations
Yajuan Cao
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Yangpu District, Shanghai 200433, China
Yonghui Wu
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Yangpu District, Shanghai 200433, China; Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Hongbin Tu
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Yangpu District, Shanghai 200433, China
Zhan Gu
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Yangpu District, Shanghai 200433, China
Fengzhi Yu
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Yangpu District, Shanghai 200433, China
Weiling Huang
Shanghai Jing 'an District Hospital of Traditional Chinese Medicine, Shanghai 200072, China
Liping Shen
LongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Lixin Wang
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Yangpu District, Shanghai 200433, China; Corresponding author.
Yan Li
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China; Corresponding author.
In the context of cancer expansion, epithelial-mesenchymal transition (EMT) plays an essential role in driving invasion and metastasis potential of cancer cells. Tumor-associated macrophages (TAMs)-derived factors involved in the initiation and progression of EMT. We assess the role of M2 macrophage in suppressing lung tumors of a natural compound (−)-Guaiol by using macrophage depleted model. Bone marrow-derived monocytes (BMDMs) were extracted and induced to M2-like phenotype in vitro. The co-culture of M2 macrophage and lung cancer cells was established to observe that inhibition of lung tumor growth by (−)-Guaiol requires presence of macrophages. This suppressed effect of (−)-Guaiol was alleviated when mice macrophage was depleted. The expression of M2-like macrophages was strongly reduced by (−)-Guaiol treated mice, but not the changes of M1-like macrophages. In vitro studies, we demonstrated that (−)-Guaiol suppressed M2 polarization of BMDMs, as well as migration, invasion, and EMT of lung cancer cells in co-culture. M2 macrophage-derived interleukin 10 (IL-10) was investigated as a critical signaling molecule between M2 macrophage and lung cancer cells. We have also verified that the mechanism of (−)-Guaiol inhibiting the EMT process of lung cancer is related to the activation of IL-10-mediated signal transducer and activator of transcription 3 (STAT3). These results suggested that the suppressive effect role of (−)-Guaiol in M2 macrophage promoting EMT of lung cancer, which was associated with inhibition of IL-10 mediated STAT3 signaling pathway.
