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The Anti-fibrosis drug Pirfenidone modifies the immunosuppressive tumor microenvironment and prevents the progression of renal cell carcinoma by inhibiting tumor autocrine TGF-β
- Source :
- Cancer Biology & Therapy, Vol 23, Iss 1, Pp 150-162 (2022)
- Publication Year :
- 2022
- Publisher :
- Taylor & Francis Group, 2022.
-
Abstract
- Transforming growth factor-β (TGF-β) plays a critical role in regulating cell growth and differentiation. Epithelial to mesenchymal transition (EMT) induced by TGF-β promotes cancer cell migration, invasion, and proliferation. Pirfenidone (5-methyl-1-phenyl-2(1 H)-pyridone, PFD), an approved drug for treating pulmonary and renal fibrosis, is a potent TGF-β inhibitor and found reduced incidence of lung cancer and alleviated renal function decline. However, whether PFD plays a role in controlling renal cancer progression is largely unknown. In the present study, we demonstrated that high TGF-β1 expression was negatively associated with ten-year overall survival of patients with renal cancer. Functionally, blockade of TGF-β signaling with PFD significantly suppressed the progression of renal cancer in a murine model. Mechanistically, we revealed that PFD significantly decreased the expression and secretion of TGF-β both in vitro and in vivo tumor mouse model, which further prevented TGF-β-induced EMT and thus cell proliferation, migration, and invasion. Importantly, the downregulation of TGF-β upon PFD treatment shaped the immunosuppressive tumor microenvironment by limiting the recruitment of tumor-infiltrating MDSCs. Therefore, our study demonstrated that PFD prevents renal cancer progression by inhibiting TGF-β production of cancer cells and downstream signaling pathway, which might be presented as a therapeutic adjuvant for renal cancer.
Details
- Language :
- English
- ISSN :
- 15384047 and 15558576
- Volume :
- 23
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cancer Biology & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.73b030e57dbc4d289c244bb1a9138104
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/15384047.2022.2035629