Hepatocellular carcinoma (HCC) is the primary tumor of the liver and the fourth leading cause of cancer-related death. Recently, several studies indicated the anti-tumor potential of antipsychotic medicine. Quetiapine, an atypical antipsychotic, is used to treat schizophrenia, bipolar disorder, and major depressive disorder since 1997. However, whether quetiapine may show potential to suppress HCC progression and its underlying mechanism is persisting unclear. Quetiapine has been shown to induce apoptosis and inhibit invasion ability in HCC in vitro. Here, we established two different HCC (Hep3B, SK-Hep1) bearing animals to identify the treatment efficacy of quetiapine. Tumor growth, signaling transduction, and normal tissue pathology after quetiapine treatment were validated by caliper, bioluminescence image, immunohistochemistry (IHC), and hematoxylin and eosin staining, respectively. Quetiapine suppressed HCC progression in a dose-dependent manner. Extracellular signal-regulated kinases (ERKs) and Nuclear factor-κB (NF-κB) mediated downstream proteins, such as myeloid leukemia cell differentiation protein (MCL-1), cellular FLICE-inhibitory protein (C-FLIP), X-linked inhibitor of apoptosis protein (XIAP), Cyclin-D1, matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor-A (VEGF-A) and indoleamine 2,3-dioxygenase (IDO) which involved in proliferation, survival, angiogenesis, invasion and anti-tumor immunity were all decreased by quetiapine. In addition, extrinsic/intrinsic caspase-dependent and caspase-independent pathways, including cleaved caspase-3, −8, and − 9 were increased by quetiapine. In sum, the tumor inhibition that results from quetiapine may associate with ERK and NF-κB inactivation.

中文翻译：

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喹硫平对体内肝细胞癌肿瘤进展的抑制作用及机制

肝细胞癌（HCC）是肝脏的原发性肿瘤，也是癌症相关死亡的第四大原因。最近，一些研究表明抗精神病药物的抗肿瘤潜力。喹硫平是一种非典型抗精神病药，自 1997 年以来一直用于治疗精神分裂症、双相情感障碍和重度抑郁症。然而，喹硫平是否可能显示出抑制 HCC 进展的潜力，其潜在机制仍不清楚。已显示喹硫平在体外诱导 HCC 细胞凋亡并抑制侵袭能力。在这里，我们建立了两种不同的 HCC (Hep3B, SK-Hep1) 动物来确定喹硫平的治疗效果。通过卡尺、生物发光图像、免疫组织化学 (IHC)、和苏木精和伊红染色，分别。喹硫平以剂量依赖性方式抑制 HCC 进展。细胞外信号调节激酶 (ERK) 和核因子-κB (NF-κB) 介导的下游蛋白，如髓性白血病细胞分化蛋白 (MCL-1)、细胞 FLICE 抑制蛋白 (C-FLIP)、X 连锁抑制剂凋亡蛋白 (XIAP)、细胞周期蛋白-D1、基质金属肽酶 9 (MMP-9)、血管内皮生长因子-A (VEGF-A) 和吲哚胺 2,3-双加氧酶 (IDO)，它们参与增殖、存活、血管生成，喹硫平可降低侵袭力和抗肿瘤免疫力。此外，喹硫平增加了外在/内在 caspase 依赖性和 caspase 非依赖性途径，包括切割的 caspase-3、-8 和 -9。总共，