Vortioxetine is a potent antagonist of the 5‐hydroxytryptamine receptor and serotonin transporter and has been reported to function as an antidepressant in the treatment of major depressive disorder. However, its antitumor effects remain unclear. Here, we examined whether vortioxetine affects the characteristics of GC cells. Cell viability was measured by a colony formation assay and, in addition, cell invasion, migration and apoptosis assays were performed with a transwell assay and a flow cytometry assay. Protein levels were measured by western blotting. We found that vortioxetine inhibited the proliferation, invasion and migration abilities of AGS cells. Additionally, vortioxetine could induce apoptosis and autophagy by increasing the levels of Bax, active caspase‐3/‐9, Beclin‐1 and light chain 3, as well as by downregulating Bcl‐2 and P62. Further investigations indicated that vortioxetine regulated apoptosis and autophagy via activation of the phosphoinositide 3‐kinase/AKT pathway. Taken together, our data suggest that vortioxetine has cytotoxic effects against GC AGS cells as a result of inhibiting proliferation, invasion and migration, as well as by inducing apoptosis and autophagy through the phosphoinositide 3‐kinase/AKT pathway.

中文翻译：

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Vortioxetine 通过 PI3K/AKT 通路诱导胃癌 AGS 细胞凋亡和自噬。

Vortioxetine 是 5-羟色胺受体和 5-羟色胺转运蛋白的强效拮抗剂，据报道可作为抗抑郁药治疗重度抑郁症。然而，其抗肿瘤作用仍不清楚。在这里，我们检查了 vortioxetine 是否影响 GC 细胞的特性。通过集落形成测定法测量细胞活力，此外，通过transwell测定法和流式细胞术测定法进行细胞侵袭、迁移和凋亡测定。通过蛋白质印迹测量蛋白质水平。我们发现vortioxetine抑制AGS细胞的增殖、侵袭和迁移能力。此外，vortioxetine 可通过增加 Bax、活性 caspase-3/-9、Beclin-1 和轻链 3 的水平以及下调 Bcl-2 和 P62 来诱导细胞凋亡和自噬。进一步的研究表明，vortioxetine 通过激活磷酸肌醇 3-激酶/AKT 通路来调节细胞凋亡和自噬。总之，我们的数据表明，由于抑制增殖、侵袭和迁移，以及通过磷酸肌醇 3-激酶/AKT 途径诱导细胞凋亡和自噬，vortioxetine 对 GC AGS 细胞具有细胞毒性作用。