Prajumwongs Piya, Waenphimai Orawan, Vaeteewoottacharn Kulthida, Wongkham Sopit, Sawanyawisuth Kanlayanee
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
PeerJ. 2021 Jan 7;9:e10637. doi: 10.7717/peerj.10637. eCollection 2021.
Reversine is a selective inhibitor of mitotic kinase monopolar spindle 1 (MPS1) and has been reported as an anticancer agent in various cancers. The effects of reversine on bile duct cancer, cholangiocarcinoma (CCA), a lethal cancer in Northeastern Thailand, were investigated. This study reports that reversine inhibited cell proliferation of CCA cell lines in dose- and time-dependent manners but had less inhibitory effect on an immortalized cholangiocyte cell line. Reversine also triggered apoptotic cell death by decreasing anti-apoptotic proteins, Bcl-XL and Mcl-1, increasing Bax pro-apoptotic protein and activating caspase-3 activity. Moreover, reversine induced autophagic cell death by increasing LC3-II and Beclin 1 while decreasing p62. Reversine activated autophagy via the AKT signaling pathway. Additionally, this study demonstrated for the first time that reversine could diminish the expression of Hypoxia-Inducible Factor 1- alpha (HIF-1) and glucose transporter 1 (GLUT1), resulting in a reduction of glucose uptake and energy production in CCA cell lines. These findings suggest that reversine could be a good candidate as an alternative or supplementary drug for CCA treatment.
逆转素是有丝分裂激酶单极纺锤体1（MPS1）的选择性抑制剂，已被报道为多种癌症的抗癌剂。本研究调查了逆转素对泰国东北部致命癌症胆管癌（CCA）的影响。该研究报告称，逆转素以剂量和时间依赖性方式抑制CCA细胞系的细胞增殖，但对永生化胆管细胞系的抑制作用较小。逆转素还通过减少抗凋亡蛋白Bcl-XL和Mcl-1、增加促凋亡蛋白Bax并激活caspase-3活性来触发凋亡性细胞死亡。此外，逆转素通过增加LC3-II和Beclin 1同时减少p62来诱导自噬性细胞死亡。逆转素通过AKT信号通路激活自噬。此外，本研究首次证明逆转素可以减少缺氧诱导因子1-α（HIF-1）和葡萄糖转运蛋白1（GLUT1）的表达，从而导致CCA细胞系中葡萄糖摄取和能量产生的减少。这些发现表明，逆转素可能是一种很好的候选药物，可作为CCA治疗的替代或补充药物。
