Yue Haiying, Huang Dongning, Qin Li, Zheng Zhiyong, Hua Li, Wang Guodong, Huang Jian, Huang Haixin
Department of Oncology, Liuzhou City Workers Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545000, China.
Biomed Res Int. 2016;2016:6709828. doi: 10.1155/2016/6709828. Epub 2016 Jul 31.
Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells.
肺癌干细胞是对肺癌进展、转移和耐药性至关重要的细胞亚群。硫利达嗪是一种经典的神经药物，已被报道具有抗癌能力。然而，硫利达嗪是否能抑制肺癌干细胞从未被研究过。在我们目前的工作中，我们使用不同剂量的硫利达嗪来测试其对肺癌干细胞球形成的影响。测量了硫利达嗪处理后肺癌干细胞对化疗药物的反应。检测了硫利达嗪处理后肺癌干细胞的细胞周期分布。还测量了硫利达嗪的体内抑制作用。我们发现硫利达嗪能显著抑制肺癌干细胞的球形成。它使肺癌干细胞对化疗药物5-氟尿嘧啶和顺铂敏感。硫利达嗪改变了肺癌干细胞的细胞周期分布，降低了肺癌干细胞中G0期细胞的比例。硫利达嗪在体内抑制肺癌干细胞引发的肿瘤生长。这项研究表明硫利达嗪在体外和体内都能抑制肺癌干细胞。它通过靶向肺癌干细胞为肺癌治疗提供了一种潜在的药物。
