Shen Jiani, Ma Buyun, Zhang Xinmin, Sun Xiaozhu, Han Jiancui, Wang Yigang, Chu Liang, Xu Haineng, Yang Yu
Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P.R. China.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, P.R. China.
Oncol Lett. 2017 Mar;13(3):1563-1568. doi: 10.3892/ol.2017.5651. Epub 2017 Jan 25.
Thioridazine (TDZ), originally an anti-psychotic drug, suppresses several types of cancer and has specificity for leukemia stem cells. The present study was performed to assess its effect on lung cancer stem-like cells, as its effect remains unknown. TDZ was utilized to treat lung cancer stem-like cells (A549 sphere cells) and its cytotoxic effect and mechanism were evaluated and . TDZ elicited cytotoxicity in A549 sphere cells and inhibited their proliferation in a dose-dependent pattern. A549 sphere cells treated with TDZ showed nuclear fragmentation, increased G0/G1 phase distribution, positive Annexin V staining, and a change in the expression of caspase family and cell cycle-associated proteins. These results suggest the induction of caspase-dependent apoptosis and cell cycle arrest. In addition, TDZ treatment resulted in significant inhibitory effect on mice xenografts established by A549 sphere cells. TDZ repressed growth of lung cancer stem-like cells and , indicating its potential application in targeting lung cancer stem-like cells.
硫利达嗪（TDZ）最初是一种抗精神病药物，可抑制多种类型的癌症，并且对白血病干细胞具有特异性。由于其对肺癌干细胞样细胞的作用尚不清楚，因此进行了本研究以评估其对肺癌干细胞样细胞的影响。使用TDZ处理肺癌干细胞样细胞（A549球形细胞），并评估其细胞毒性作用和机制。TDZ在A549球形细胞中引发细胞毒性，并以剂量依赖性方式抑制其增殖。用TDZ处理的A549球形细胞显示核碎裂、G0/G1期分布增加、膜联蛋白V染色阳性以及半胱天冬酶家族和细胞周期相关蛋白表达的变化。这些结果表明诱导了半胱天冬酶依赖性凋亡和细胞周期停滞。此外，TDZ处理对由A549球形细胞建立的小鼠异种移植瘤产生了显著的抑制作用。TDZ抑制肺癌干细胞样细胞的生长，表明其在靶向肺癌干细胞样细胞方面的潜在应用。
