Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer
Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer
复制标题
抗精神病药匹莫齐特通过诱导肝癌细胞静止来促进可逆性增殖抑制。
DOI：
10.3892/or.2019.7229
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发表时间：
2019-09-01
期刊：
影响因子：
4.2
通讯作者：
Ji, Kunmei
中科院分区：
文献类型：
--
作者：
Chen, Jia-Jie;Zhang, Li-Na;Ji, Kunmei
抗精神病药物吡莫胺已被发现具有抗癌作用。先前有研究表明，吡莫胺可抑制肝细胞癌（HCC）细胞生长，但其药效学特性尚不清楚。本研究的目的是探讨吡莫胺抑制肝癌细胞增殖能力的可逆性及其机制。采用细胞计数试剂盒-8和菌落形成法测定细胞活力。流式细胞术Ki-67和PI染色分析细胞周期分布。DCFH-DA检测肝癌细胞的ROS生成，NAC抑制其生成。Western blot检测相关信号分子在HCC细胞中的表达。我们的研究结果显示，匹莫齐特促进HCC细胞系的G0/G1期阻滞，但没有明显的细胞死亡。其对HCC细胞的抗增殖作用是可逆的，与参与细胞静止和活性氧（ROS）的产生一致。吡莫齐特增强索拉非尼对HCC细胞增殖的抑制作用。总之，阐明吡莫齐在肝癌中的可逆性增殖抑制作用及其与一种成熟的抗癌药物的附加活性，值得进一步探索吡莫齐作为辅助抗癌治疗的潜力。
The antipsychotic drug pimozide has been found to exhibit anticancer effects. Previously, it was demonstrated that pimozide inhibits hepatocellular carcinoma (HCC) cell growth, but its pharmacodynamic characteristics remain unclear. The aim of the present study was to investigate the reversibility and mechanism of the ability of pimozide to inhibit cell proliferation in liver cancer. Cell viability was determined by Cell Counting Kit-8 and colony formation assay. The cell cycle distribution was analyzed by flow cytometry with Ki-67 and PI staining. ROS production of HCC cells was detected with DCFH-DA and inhibited with NAC treatment. Western blot assay was performed to detect the expression of related signaling molecules in HCC cells. Our results showed that pimozide promoted G0/G1 phase arrest in HCC cell lines without significant cell death. Its anti-proliferative effects on HCC cells were reversible, consistent with involvement of cell quiescence and reactive oxygen species (ROS) production. Pimozide enhanced inhibition of HCC cell proliferation by sorafenib. In conclusion, elucidation of pimozide's reversible proliferation inhibition in liver cancer and additive activity with a well-established anticancer drug warrants further exploration of the potential of pimozide as an adjuvant anticancer therapy.