The Anti-fibrosis drug Pirfenidone modifies the immunosuppressive tumor microenvironment and prevents the progression of renal cell carcinoma by inhibiting tumor autocrine TGF-β.
The Anti-fibrosis drug Pirfenidone modifies the immunosuppressive tumor microenvironment and prevents the progression of renal cell carcinoma by inhibiting tumor autocrine TGF-β.
复制标题
抗纤维化药物 Pirfenidone 通过抑制肿瘤自分泌 TGF-β 来改变免疫抑制肿瘤微环境并防止肾细胞癌的进展。
DOI：
10.1080/15384047.2022.2035629
复制
发表时间：
2022-12-31
影响因子：
3.6
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Wang G;Zhou X;Guo Z;Huang N;Li J;Lv Y;Han L;Zheng W;Xu D;Chai D;Li H;Li L;Zheng J
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.
登录
查看更多内容
影响因子：
11.2
作者：
Le Scolan, Erwan;Zhu, Qingwei;Luo, Kunxin
通讯作者：
Luo, Kunxin
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D
DOI：
10.1016/j.bbrc.2016.07.124
发表时间：
2016-09-16
影响因子：
3.1
作者：
Kim, Jiyeon;Kim, Tae Yeon;Kim, Soon Ae
通讯作者：
Kim, Soon Ae
Costunolide 通过调节 NF-kB 和 TGF-beta(1)/Smad(2)/Nrf(2)-NOX4 信号通路抑制肺纤维化
DOI：
10.1016/j.bbrc.2019.01.104
发表时间：
2019-03-05
影响因子：
3.1
作者：
Liu, Bin;Rong, Yumei;Wang, Taoyuan
通讯作者：
Wang, Taoyuan
影响因子：
30.8
作者：
Colmenares, C;Heilstedt, HA;Stavnezer, E
通讯作者：
Stavnezer, E