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Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages.
- Source :
-
Pharmacological Research . Jul2018, Vol. 133, p121-131. 11p. - Publication Year :
- 2018
-
Abstract
- Although M2-like tumor-associated macrophages (TAMs) have been considered as a vital therapeutic target in cancer therapy due to their role in promoting tumor progression and metastasis, very few compounds have been identified to inhibit M2-like polarization of TAMs. Here, we showed that Imatinib significantly prevented macrophage M2-like polarization induced by IL-13 or IL-4 in vitro, as illustrated by reduced expression of cell surface marker CD206 and M2-like genes, including Arg1, Mgl2, Mrc1, CDH1, and CCL2. Further, the migration of lung cancer cells promoted by the conditioned medium from M2-like macrophages could be restrained by Imatinib. Mechanistically, Imatinib inhibited STAT6 phosphorylation and nuclear translocation, resulting in the macrophage M2-like polarization arrest. Furthermore, Imatinib reduced the number of metastasis of Lewis lung cancer without affecting tumor growth. Both in tumor and lung tissues, the percentage of M2-like macrophages decreased after the administration of Imatinib for one week. Taken together, these data suggest that Imatinib is able to inhibit macrophage M2-like polarization, which plays a vital role in Imatinib suppressed metastasis of Lewis lung cancer. [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMATINIB
*LUNG cancer
*METASTASIS
*MACROPHAGES
*PHOSPHORYLATION
Subjects
Details
- Language :
- English
- ISSN :
- 10436618
- Volume :
- 133
- Database :
- Academic Search Index
- Journal :
- Pharmacological Research
- Publication Type :
- Academic Journal
- Accession number :
- 130643011
- Full Text :
- https://doi.org/10.1016/j.phrs.2018.05.002