期刊
ONCOLOGY REPORTS
卷 31, 期 5, 页码 2107-2114出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3068
关键词
thioridazine; antipsychotic drug; gastric cancer; apoptosis; caspase; mitochondria; in vivo
类别
资金
- National Natural Science Foundation of China [81172026, 81272402, 81301816, 81172029]
- Foundation of Shanghai Outstanding Academic Leaders [11XD1403800]
- National High Technology Research and Development Program (863 Program) [2012AA022606]
- Post-doctoral Research Foundation of China [2012M511107]
- Foundation for Interdisciplinary Research of Shanghai Jiao Tong University [YG2011ZD07]
- Shanghai Science and Technology Commission Inter-governmental International Cooperation Project [12410705900]
- Shanghai Science and Technology Commission Medical-Guiding Project [12401905800]
- Program for Changjiang Scholars
- Post-doctoral Research Program of Shanghai [12R21415300]
Thioridazine, an antipsychotic drug, has been reported to induce apoptosis in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs). However, whether it elicits anticancer effects in gastric cancer has never been reported. In the present study, we examined the ability of thioridazine to induce cell death in the gastric cancer cell lines NCI-N87 and AGS, and detected its in vivo tumor inhibition capacity. Thioridazine elicited cytotoxic effects on NCI-N87 and AGS cells in a dose-dependent manner, and inhibited the colony formation abilitiy of the NCI-N87 and AGS cells. Thioridazine treatment induced nuclear fragmentation, increased the proportion of sub-G1 phase cells, and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. Moreover, thioridazine induced gastric cancer cell apoptosis in a caspase-dependent manner, as shown by a decrease in the precursors of casapse-9, caspase-8 and caspase-3, and by the ability of the caspase inhibitor Z-VAD-FMK to reverse the cytotoxic effect of thioridazine. JC-1 staining further revealed that thioridazine induced gastric cancer cell apoptosis via the mitochondrial pathway. In addition, thioridazine pretreatment inhibited the growth of NCI-N87 cell-derived tumors. The present study demonstrated that the antipsychotic drug thioridazine possesses anti-gastric cancer ability through in vitro and in vivo experiments, suggesting thioridazine as a potential drug in gastric cancer therapy.
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