An Qi, Zhou Yan, Han Chao, Zhou Yubing, Li Feng, Li Duolu
1 Department of Clinical Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
2 Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Reprod Sci. 2017 Oct;24(10):1462-1468. doi: 10.1177/1933719117691143. Epub 2017 Feb 9.
Epithelial ovarian cancer (EOC) is the leading cause of cancer-related death among all the gynecological malignancies of the female genital system, and its incidence and mortality rates continue to rise. B-cell translocation gene 3 (BTG3) plays an important role in the occurrence and development of numerous cancers. However, the role of BTG3 in EOC remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of BTG3 in EOC. We found that BTG3 protein expression was significantly lower in human EOC cell lines. Next, BTG3 upregulation by transfection with pcDNA3.1-BTG inhibited cell proliferation and invasion but promoted cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. In addition, BTG3 knockdown by small interfering RNA promoted cell proliferation and invasion, but inhibited cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. Importantly, several proteins, including phosphorylation serine/threonine kinase (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β), and β-catenin, were markedly decreased by BTG3 upregulation, whereas increased by BTG3 knockdown. Taken together, the results of our study suggest that BTG3 overexpression could inhibit cell proliferation and invasion and promotes cell apoptosis in EOC cell, possibly by regulating the AKT/GSK3β/β-catenin signaling pathway, providing novel insights into the treatment of EOC through BTG3 overexpression.
上皮性卵巢癌（EOC）是女性生殖系统所有妇科恶性肿瘤中癌症相关死亡的主要原因，其发病率和死亡率持续上升。B细胞易位基因3（BTG3）在众多癌症的发生和发展中起重要作用。然而，BTG3在EOC中的作用仍知之甚少。在本研究中，我们旨在探讨BTG3在EOC中的生物学作用及潜在分子机制。我们发现BTG3蛋白在人EOC细胞系中的表达显著降低。接下来，用pcDNA3.1-BTG转染上调BTG3可抑制2种人EOC细胞系SKOV-3和HO-8910细胞的增殖和侵袭，但促进细胞凋亡。此外，用小干扰RNA敲低BTG3可促进2种人EOC细胞系SKOV-3和HO-8910细胞的增殖和侵袭，但抑制细胞凋亡。重要的是，上调BTG3可使包括磷酸化丝氨酸/苏氨酸激酶（p-AKT）、磷酸化糖原合酶激酶3β（p-GSK3β）和β-连环蛋白在内的几种蛋白明显减少，而敲低BTG3则使其增加。综上所述，我们的研究结果表明，BTG3过表达可能通过调节AKT/GSK3β/β-连环蛋白信号通路抑制EOC细胞的增殖和侵袭并促进细胞凋亡，为通过BTG3过表达治疗EOC提供了新的见解。
