Yu Ai-Song, Zhao Lin
Department of Preventive Medicine, School of Public Health, Dalian Medical University, Dalian, 116044, People's Republic of China.
Department of Breast Surgery, Liaoning Cancer Hospital & Institute, Shenyang, 110042, People's Republic of China.
Tumour Biol. 2016 Apr;37(4):4857-64. doi: 10.1007/s13277-015-4344-8. Epub 2015 Nov 2.
Ovarian cancer (OC) is a deadly disease, and despite improvements in treatment, overall 5-year survival is low. Glycogen synthase kinase (GSK)-3β is a multifunctional serine/threonine kinase. We wished to ascertain if the GSK-3β inhibitor (2Z,3E)-6-bromoindirubin-3'-oxime, known as "BIO," can suppress OC development. The OC cell lines A2780 and OVCAR3 were exposed to BIO. At different time points, cell proliferation, apoptosis, cell cycle, and cell invasion/cell migration assays were carried out. Phalloidin staining was undertaken to observe lamellipodia formation. Real-time reverse transcription-polymerase chain reaction and western blotting were used to assess expression of messenger RNA (mRNA) and protein of GSK-3β, cyclin D1, matrix metalloproteinase (MMP)-9, and p21. BIO suppressed the proliferation, invasion, and migration of OC cells; reduced lamellipodia formation; and induced G1 arrest of the cell cycle. BIO exposure led to a significant downregulation of mRNA and protein expression of cyclin D1 and MMP9 in comparison with untreated control cells. In contrast, BIO exposure upregulated mRNA and protein expression of p21 in comparison with untreated control cells. Besides, GSK-3β small interfering RNA (siRNA) transfection in ovarian cancer cells also downregulated GSK-3β, cyclin D1, and MMP9 protein expression while upregulated p21 expression. These data suggest that BIO, as an inhibitor of GSK-3β, can suppress OC development. Therefore, BIO could be a candidate drug for the treatment of OC.
卵巢癌（OC）是一种致命疾病，尽管治疗有所改善，但总体5年生存率仍然很低。糖原合酶激酶（GSK）-3β是一种多功能丝氨酸/苏氨酸激酶。我们希望确定GSK-3β抑制剂（2Z，3E）-6-溴靛玉红-3'-肟，即“BIO”，是否能抑制OC的发展。将OC细胞系A2780和OVCAR3暴露于BIO。在不同时间点进行细胞增殖、凋亡、细胞周期以及细胞侵袭/细胞迁移实验。采用鬼笔环肽染色观察片状伪足的形成。使用实时逆转录-聚合酶链反应和蛋白质印迹法评估GSK-3β、细胞周期蛋白D1、基质金属蛋白酶（MMP）-9和p21的信使核糖核酸（mRNA）和蛋白质表达。BIO抑制了OC细胞的增殖、侵袭和迁移；减少了片状伪足的形成；并诱导细胞周期的G1期阻滞。与未处理的对照细胞相比，BIO处理导致细胞周期蛋白D1和MMP9的mRNA和蛋白质表达显著下调。相反，与未处理的对照细胞相比，BIO处理上调了p21的mRNA和蛋白质表达。此外，在卵巢癌细胞中进行GSK-3β小干扰RNA（siRNA）转染也下调了GSK-3β、细胞周期蛋白D1和MMP9的蛋白质表达，同时上调了p21的表达。这些数据表明，作为GSK-3β抑制剂的BIO可以抑制OC的发展。因此，BIO可能是一种治疗OC的候选药物。
