Department of Urology, Zhenhai People's Hospital, Ningbo, Zhejiang, China.
Department of Urology, Zhenhai People's Hospital, Ningbo, Zhejiang, China.
Biochem Biophys Res Commun. 2022 May 14;604:165-171. doi: 10.1016/j.bbrc.2022.03.029. Epub 2022 Mar 7.
Bladder cancer (BC) is a common malignancy of the urological system that still lacks effective treatment. It is frequently characterised by dysregulation of fibroblast growth factor receptor (FGFR) signalling. FGFR inhibitors have been proven as a promising treatment for BC in clinical settings. Besides the FGFR signalling, the therapeutic effects of FGFR inhibitors are often limited owing to various mechanisms, such as the activation of the Akt signalling pathway. Therefore, this study aimed to examine the synergistic effects of ipatasertib, a FGFR inhibitor, and erdafitinib, an Akt inhibitor, in BC cells. Ipatasertib and erdafitinib co-treatment synergistically inhibited cell proliferation and induced BC cell death. Mechanically, ipatasertib and erdafitinib induced the activation of Bax, an essential protein for cell death. Moreover, erdafitinib, which inhibited the Akt signalling pathway, is responsible for Bim upregulation, a condition critical to achieving the synergistic effects. Therefore, our data suggest that ipatasertib and erdafitinib co-treatment is a promising strategy for BC.
膀胱癌（BC）是一种常见的泌尿系统恶性肿瘤，目前仍缺乏有效的治疗方法。其特征通常是成纤维细胞生长因子受体（FGFR）信号通路失调。FGFR 抑制剂已被证明在临床环境中是治疗 BC 的一种有前途的方法。除 FGFR 信号通路外，FGFR 抑制剂的治疗效果通常受到多种机制的限制，例如 Akt 信号通路的激活。因此，本研究旨在研究 FGFR 抑制剂伊帕替尼（ipatasertib）和 Akt 抑制剂 erdafitinib 在 BC 细胞中的协同作用。伊帕替尼和 erdafitinib 联合治疗可协同抑制细胞增殖并诱导 BC 细胞死亡。在机制上，伊帕替尼和 erdafitinib 诱导 Bax 的激活，Bax 是细胞死亡的关键蛋白。此外，抑制 Akt 信号通路的 erdafitinib 负责 Bim 的上调，这是实现协同作用的关键条件。因此，我们的数据表明，伊帕替尼和 erdafitinib 联合治疗是治疗 BC 的一种有前途的策略。
