Background/Aim: Quetiapine, an atypical antipsychotic, has been encountered as a potential protective agent to suppress various types of tumor growth. However, the inhibitory mechanism of quetiapine in hepatocellular carcinoma (HCC) still remains unclear. The purpose of present study was to investigate the inhibitory mechanism of quetiapine on cell survival and invasion in HCC. Materials and Methods: Changes of apoptotic signaling, migration/invasion ability, and signaling transduction involved in cell survival and invasion were evaluated with flow cytometry, migration/invasion, and western blot assays. Results: Quetiapine inhibited cell proliferation and migration/invasion in SK-Hep1 and Hep3B cells. Quetiapine induced extrinsic and intrinsic apoptotic pathways. Activation of extracellular signal-regulated kinases (ERK), protein kinase B (AKT), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), expression of anti-apoptotic, and metastasis-associated proteins were decreased by quetiapine. Conclusion: The apoptosis induction, the decreased expression of ERK/AKT-mediated anti-apoptotic and the metastasis-associated proteins were associated with quetiapine-inhibited cell survival and invasion in HCC in vitro.

中文翻译：

---

ERK/AKT 失活和凋亡诱导与喹硫平抑制的肝细胞癌细胞存活和侵袭有关

背景/目的：喹硫平是一种非典型抗精神病药，已被用作抑制各种类型肿瘤生长的潜在保护剂。然而，喹硫平在肝细胞癌（HCC）中的抑制机制仍不清楚。本研究的目的是探讨喹硫平对肝癌细胞存活和侵袭的抑制机制。材料和方法：使用流式细胞术、迁移/侵袭和蛋白质印迹分析评估凋亡信号、迁移/侵袭能力和参与细胞存活和侵袭的信号转导的变化。结果：喹硫平抑制 SK-Hep1 和 Hep3B 细胞的细胞增殖和迁移/侵袭。喹硫平诱导外源性和内源性细胞凋亡途径。激活细胞外信号调节激酶 (ERK)、蛋白激酶 B (AKT)、喹硫平降低了活化 B 细胞 (NF-ĸB) 的核因子 kappa 轻链增强子、抗凋亡和转移相关蛋白的表达。结论：凋亡诱导、ERK/AKT 介导的抗凋亡和转移相关蛋白的表达降低与喹硫平抑制的肝癌体外细胞存活和侵袭有关。