Fako Valerie, Yu Zhipeng, Henrich Curtis J, Ransom Tanya, Budhu Anuradha S, Wang Xin W
1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
2. Molecular Targets Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA;; 3. Basic Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
Int J Biol Sci. 2016 Apr 28;12(7):768-75. doi: 10.7150/ijbs.14718. eCollection 2016.
Hepatocellular carcinoma (HCC) is one of the most common forms of malignant cancers in the world, yet very few effective systemic treatments for HCC patients exist. Thus, the development of new treatment modalities presents a great need. The wnt/β-catenin signaling pathway is highly activated in stem cell-like aggressive HCC, which is associated with chemoresistance and poor survival in HCC patients. In a previous study, we found that an FDA-approved psychiatric drug, pimozide (PMZ), has anti-cancer properties in HCC cell lines that express epithelial cell adhesion molecule (EpCAM), a hepatic stem cell marker that is a functional down-stream target of the wnt/β-catenin pathway. In this study, we demonstrate that PMZ effectively inhibits cell growth of HCC cells by disrupting the wnt/β-catenin signaling pathway and reducing EpCAM expression. Thus, PMZ may be a useful molecular entity that could be repurposed as an anti-cancer therapy for treatment of HCC.
肝细胞癌（HCC）是全球最常见的恶性肿瘤形式之一，但针对HCC患者的有效全身治疗方法却非常少。因此，开发新的治疗方式具有迫切需求。Wnt/β-连环蛋白信号通路在干细胞样侵袭性HCC中高度激活，这与HCC患者的化疗耐药性和较差的生存率相关。在先前的一项研究中，我们发现一种美国食品药品监督管理局（FDA）批准的精神科药物匹莫齐特（PMZ），在表达上皮细胞粘附分子（EpCAM）的HCC细胞系中具有抗癌特性，EpCAM是一种肝干细胞标志物，是Wnt/β-连环蛋白通路的功能性下游靶点。在本研究中，我们证明PMZ通过破坏Wnt/β-连环蛋白信号通路并降低EpCAM表达，有效抑制HCC细胞的生长。因此，PMZ可能是一种有用的分子实体，可重新用作治疗HCC的抗癌疗法。
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