妥富腦使膀胱癌細胞的纖維母細胞生長因子受體1失活並透過外在和內在途徑引動細胞凋亡

Imipramine Inactivates FGFR1 and Triggers Apoptosis Through Extrinsic and Intrinsic Pathways in Bladder Cancer Cells

妥富腦（imipramine）是三環抗憂鬱劑（tricyclic antidepressants, TCA）。除了其主要用途是改善抑鬱症狀外，亦被視為治療尿失禁的一種潛在替代選擇。妥富腦被指出可以抑制口腔癌和肺癌的生長。然而，妥富腦對於抗膀胱癌的潛在效應目前仍不明確。因此，本研究旨在評估妥富腦對膀胱癌細胞的抑制作用，並探討其可能的作用機制。膀胱癌細胞MB49和T24被處理（0–100μM）妥富腦並培養24和48小時。細胞存活試驗的結果顯示，妥富腦能夠有效地減緩膀胱癌細胞的生長。流式細胞儀分析表明，妥富腦能夠顯著增加cleaved caspase-3、-8和-9的活性，同時促進粒線體膜電位的下降和活性氧類的累積。西方墨點法顯示，妥富腦顯著抑制MB49和T24纖維母細胞生長因子受體1（FGFR1）的磷酸化，該受體磷酸化與膀胱癌細胞生長和侵襲有關。本次研究顯示，妥富腦能夠有效地抑制膀胱癌細胞的生長，同時抑制FGFR1的活性。此外，妥富腦透過調控外在和內在途徑促進膀胱癌細胞的細胞凋亡。

Imipramine, classified as a tricyclic antidepressant (TCA), is predominantly employed to ameliorate depressive symptoms and is also being explored as a potential option for addressing urinary incontinence. Imipramine has been shown to possess inhibitory properties against the growth of oral and lung cancers. However, the potential impact of imipramine on bladder cancer has yet to be conclusively determined. Therefore, the goal of this study is to evaluate the inhibitory effects of imipramine on bladder cancer cells and investigate the potential mechanisms underlying its actions. Bladder cancer MB49 and T24 cells were exposed to imipramine and incubated for 24 and 48 hours. Findings from cell viability assays reveal that imipramine markedly impedes the proliferation of bladder cancer cells. Flow cytometry analysis indicates that imipramine significantly increases the activity of cleaved caspase-3, -8, and -9, while promoting the loss of mitochondrial membrane potential (MMP) and the accumulation of reactive oxygen species (ROS). Constitutive activation of fibroblast growth factor receptor 1 (FGFR1) promotes the growth and invasion of bladder cancer cells. Western blot analysis indicates that imipramine significantly inhibits the phosphorylation of FGFR1 in both MB49 and T24 cells. This study demonstrates that imipramine effectively suppresses the growth of bladder cancer cells while inhibiting the activity of FGFR1. Furthermore, imipramine induces apoptosis through the regulation of both extrinsic and intrinsic pathways in bladder cancer cells.