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Resolvin D1 inhibits TGF-β1-induced epithelial mesenchymal transition of A549 lung cancer cells via lipoxin A4 receptor/formyl peptide receptor 2 and GPR32
- Source :
- The International Journal of Biochemistry & Cell Biology. 45:2801-2807
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Epithelial-mesenchymal-transition (EMT) is a key event for tumor cells to initiate metastasis which lead to switching of E-cadherin to N-cadherin. Resolvins are known to promote the resolution of inflammation and phagocytosis of macrophages. However, the role of resolvins in EMT of cancer is not known. Therefore, we examined the effects of resolvins on transforming growth factor, beta 1 (TGF-β1)-induced EMT. Expression of E-cadherin and N-cadherin in A549 lung cancer cells was evaluated by Western blot and confocal microscopy. Involvement of lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) was examined by gene silencing. TGF-β1 induced expression of N-cadherin in A549 lung cancer cells, and resolvin D1 and D2 inhibited the expression of N-cadherin at low concentrations (1-100 nM). Resolvin D1 and D2 also suppressed the expression of zinc finger E-box binding homeobox 1 (ZEB1). The effects of resolvin D1 and D2 were confirmed in other lung cancer cell lines such as H838, H1299, and H1703. Resolvin D1 and D2 did not affect the proliferation of A549 lung cancer cells. Resolvin D1 and D2 also suppressed the TGF-β1-induced morphological change. Resolvin D1 and D2 also inhibited the TGF-β1-induced migration and invasion of A549 cells. Resolvin D1 is known to act via ALX/FPR2 and GPR32. Thus, we examined the involvement of ALX/FPR2 and GPR32 in the suppressive effects of resolvin D1 on TGF-β1-induced EMT of A549 cells. Gene silencing of ALX/FPR2 and GPR32 blocked the action of resolvin D1. Overexpression of ALX/FPR2 or GPR32 increased the effects of resolvin D1. These results suggest that resolvin D1 inhibited TGF-β1-induced EMT via ALX/FPR2 and GPR32 by reducing the expression of ZEB1.
- Subjects :
- Epithelial-Mesenchymal Transition
Lung Neoplasms
Docosahexaenoic Acids
Inflammation
Transfection
CMKLR1
Biochemistry
Receptors, G-Protein-Coupled
Formyl peptide receptor 2
Transforming Growth Factor beta1
chemistry.chemical_compound
Cell Line, Tumor
medicine
Humans
Gene silencing
Epithelial–mesenchymal transition
RNA, Small Interfering
A549 cell
Cell Biology
Receptors, Formyl Peptide
Lipoxins
GPR32
chemistry
Immunology
Cancer research
medicine.symptom
Resolvin
Subjects
Details
- ISSN :
- 13572725
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- The International Journal of Biochemistry & Cell Biology
- Accession number :
- edsair.doi.dedup.....651bb1bdef5852d9dfd3256a9d22a98e