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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-ß.
Wang, Gang; Zhou, Xiaowan; Guo, Zengli; Huang, Nan; Li, Juan; Lv, Yanfang; Han, Lulu; Zheng, Wei; Xu, Dandan; Chai, Dafei; Li, Huizhong; Li, Liantao; Zheng, Junnian.
Afiliación
  • Wang G; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Zhou X; Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • Guo Z; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Huang N; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Li J; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Lv Y; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Han L; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Zheng W; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Xu D; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Chai D; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Li H; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Li L; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Zheng J; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Cancer Biol Ther ; 23(1): 150-162, 2022 12 31.
Article en En | MEDLINE | ID: mdl-35130111
Transforming growth factor-ß (TGF-ß) plays a critical role in regulating cell growth and differentiation. Epithelial to mesenchymal transition (EMT) induced by TGF-ß 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-ß 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-ß1 expression was negatively associated with ten-year overall survival of patients with renal cancer. Functionally, blockade of TGF-ß 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-ß both in vitro and in vivo tumor mouse model, which further prevented TGF-ß-induced EMT and thus cell proliferation, migration, and invasion. Importantly, the downregulation of TGF-ß 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-ß production of cancer cells and downstream signaling pathway, which might be presented as a therapeutic adjuvant for renal cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Biol Ther Asunto de la revista: NEOPLASIAS / TERAPEUTICA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Biol Ther Asunto de la revista: NEOPLASIAS / TERAPEUTICA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos