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Abstract：
Human laryngeal squamous carcinoma (LSCC) is a common malignant tumor in the head and neck. Despite the recently developed therapies for the treatment of LSCC, patients\' overall survival rate still did not enhance remarkably; this highlights the need to formulate alternative strategies to develop novel treatments. The antitumor effects of antidepressant drugs such as citalopram have been reported on several cancer cells; however, they have yet to be investigated against LSCC. The current study was directed to explore the possible antitumor effects of citalopram on human laryngeal carcinoma cell lines (HEP-2). HEP-2 cells were cultured and treated with different doses of citalopram (50-400 µM) for 24, 48, and 72 h. The effects of citalopram on the viability of cancer cells were determined by the MTT assay. In addition, apoptosis and cell cycle analysis were performed by flow cytometry. Moreover, evaluation of the expression of proapoptotic and apoptotic proteins, such as cytochrome c, cleaved caspases 3 and 9, Bcl-2, and BAX, was performed by western blotting analysis. Our results revealed that citalopram significantly suppressed the proliferation of HEP-2 cells through the upregulation of p21 expression, resulting in the subsequent arrest of the cell cycle at the G0/G1 phase. Furthermore, citalopram treatment-induced HEP-2 cell apoptosis; this was indicated by the significant increase of cytochrome c, cleaved caspases 3 and 9, and BAX protein expression. On the contrary, Bcl-2 protein expression was significantly downregulated following treatment with citalopram. The ultrastructure studies were in accordance with the protein expression findings and showed clear signs of apoptosis with ring chromatin condensation upon treatment with citalopram. These findings suggest that citalopram\'s anti-tumor activities on HEP-2 cells entailed stimulation of the intrinsic apoptotic pathway, which was mediated via Bcl-2 suppression.
摘要：
人喉鳞癌(LSCC)是头颈部常见的恶性肿瘤。尽管最近开发了治疗LSCC的疗法，患者的总体生存率仍然没有显著提高;这凸显了需要制定替代策略来开发新的治疗方法.已经报道了抗抑郁药物如西酞普兰对几种癌细胞的抗肿瘤作用；然而，他们尚未对LSCC进行调查。本研究旨在探讨西酞普兰对人喉癌细胞系（HEP-2）的可能抗肿瘤作用。将HEP-2细胞培养并用不同剂量的西酞普兰（50-400µM）处理24、48和72h。通过MTT法测定西酞普兰对癌细胞活力的影响。此外,通过流式细胞术进行细胞凋亡和细胞周期分析。此外，评估促凋亡和凋亡蛋白的表达，如细胞色素c，切割的半胱天冬酶3和9，Bcl-2和BAX，通过蛋白质印迹分析进行。我们的结果表明，西酞普兰通过上调p21表达显著抑制HEP-2细胞的增殖，导致细胞周期随后停滞在G0/G1期。此外，西酞普兰治疗诱导HEP-2细胞凋亡;这表明细胞色素c的显着增加，切割的半胱天冬酶3和9，以及BAX蛋白表达。相反,用西酞普兰治疗后，Bcl-2蛋白表达显着下调。超微结构研究与蛋白质表达结果一致，并在西酞普兰治疗后显示出明显的细胞凋亡迹象。这些发现表明，西酞普兰对HEP-2细胞的抗肿瘤活性需要刺激内在的凋亡途径，这是通过Bcl-2抑制介导的。
