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妥富腦去活化三陰性乳腺癌細胞的表皮生長因子受體信號和誘導細胞凋亡
Imipramine inactivates epidermal growth factor receptor signaling and induces apoptosis in triple-negative breast cancer cells
摘要
持續活化的表皮生長因子受體（epidermal growth factor receptor, EGFR）透過增強其下游效應蛋白質的表現，促進腫瘤進展。在三陰性乳腺癌（triple-negative breast cancer, TNBC）細胞中，EGFR失活引發生長抑制並增加對治療藥物的敏感性。妥富腦是一種三環抗抑鬱劑（tricyclic antidepressant, TCA），被指出可以下調EGFR介導非小細胞肺癌進展。然而，在TNBC細胞中，妥富腦對EGFR活性及其下游效應蛋白質的影響尚不明確。因此，本研究的主要目標是驗證妥富腦是否會抑制TNBC細胞中的EGFR活性及其下游效應蛋白質。本研究使用了TNBC MDA-MB-231和4T1細胞。將細胞處理不同濃度的妥富腦24小時。隨後，透過細胞存活試驗、流式細胞儀和西方墨點法評估細胞增生、凋亡信號、EGFR活性及其下游效應蛋白質的變化。結果顯示，妥富腦有效誘導細胞毒性和凋亡。此外，妥富腦處理導致EGFR活性降低，並減少其下游效應蛋白質的表現。結論：妥富腦對抗TNBC效應涉及誘導細胞凋亡、EGFR失活以及減少其下游效應蛋白質的表現。
並列摘要
Background/Aim: The constitutive activation of epidermal growth factor receptor (EGFR) promotes tumor progression by upregulating its downstream effector proteins. EGFR inactivation induces growth inhibition and heightens sensitivity to therapeutic agents in triple negative breast cancer (TNBC) cells. Imipramine, a tricyclic antidepressant (TCA), has been reported to downregulate the EGFR-mediated progression of non-small-cell lung cancer. However, the effect of imipramine on EGFR activity and its downstream effector proteins in TNBC cells remains ambiguous. Therefore, the primary objective of the present study was to verify whether imipramine inhibits EGFR activity and its downstream effector proteins in TNBC cells. Materials and Methods: Both TNBC MDA-MB-231 and 4T1 cells were utilized for this investigation. Cells were treated with different concentration of imipramine for 24 h. Subsequently, alterations in cell proliferation, apoptotic signaling, EGFR activity, and its downstream effector proteins were evaluated through cell viability assay, flow cytometry, and western blotting assay. Results: imipramine effectively triggered cytotoxicity and apoptosis. Additionally, the treatment with imipramine led to a reduction in both EGFR activity and its downstream effector proteins. Conclusion: the anti-TNBC effect of imipramine involves the induction of apoptosis, EGFR inactivation, and reduction of its downstream effector proteins.