title: Roles of dopamine receptors and their antagonist thioridazine in hepatoma metastasis.
abstract: Tumor metastasis is the most common cause of death and poor prognosis for cancer patients. Therapeutics that prevent tumor metastasis are the key to prolonging the lifespan of cancer patients. Cancer stem cells are believed to be critical in the metastatic process. Recently, drug screening for cancer stem cells reports that antipsychotic drugs displayed potential anticancer activity. Thioridazine, one of the antipsychotic drugs for dopamine receptors (DRs), is shown to induce the differentiation of cancer stem cells in leukemic disease and breast cancer, but it is not known if this drug would affect liver cancer. In this study, expression of DR5 was higher in tumors than in nontumor adjacent tissues, while DR1 was lower in human hepatocellular carcinoma (HCC) than those in the adjacent tissues. Other DRs were very low or undetectable. Treatment of HCC cells with thioridazine displays a dose-dependent response in HCC cell lines SNU449, LM3, and Huh7. Thioridazine treatment reduced cell viability and sphere formation of HCC cell lines through induction of G0/G1 cell cycle arrest and suppression of stemness genes CD133, OCT4, and EpCam. It also inhibited cell migration via suppression of epithelial-mesenchymal transition (EMT)-related genes such as twist2 and E-cadherin. Thioridazine-pretreated LM3 cells decreased the capacity of tumorigenesis in nude mice. Taken together, our data suggest that thioridazine may have the potential role in treatment of HCC.
authors.affiliation: Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Lu
authors.affiliation: Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, People's Republic of China ; Institution of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zaili
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Institution of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xue
authors.affiliation: Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institution of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Cunzhen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institution of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China ; Zhangjiang Center for Translational Medicine, Shanghai, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
keywords: HCC; antipsychotic; dopamine receptors; metastasis; thioridazine