Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, 1st Jianshe East Road, Zhengzhou, China.
Laboratory of Gynecological Malignant Tumor Prevention and Treatment of Henan Province, Zhengzhou, China.
Hum Cell. 2021 Jul;34(4):1197-1214. doi: 10.1007/s13577-021-00535-x. Epub 2021 Apr 27.
Ovarian cancer is the most deadly gynecological malignant tumor in the world today. Previous studies have shown that insulin-like growth factor-1 receptor (IGF-1R) is closely related to the occurrence and development of ovarian cancer, and ovarian cancer cells endogenously express high IGF-1R. Therefore, IGF-1R could be used as a target for ovarian cancer treatment. In the past, the strategy for preparing IGF-1R antagonists was to use IGF-1R antibody and small-molecule inhibitor. In the current research, we use a new method to prepare IGF-1R antagonists. We prepared a series of IGF-1 internal imaging anti-idiotypic antibodies by anti-idiotypic antibody strategy. After a series of screening and identification, one of the anti-idiotypic antibodies (B003-2A) was selected for further evaluation, and the results showed that B003-2A could not only inhibit the binding of IGF-1 to IGF-1R but also inhibit the signaling mediated by IGF-1R. Further work showed that B003-2A inhibited the proliferation of ovarian cancer cells in vivo and in vitro. In addition, the current study also indicates that B003-2A could enhance the sensitivity of cisplatin in cisplatin-resistant ovarian cancer cell lines. In summary, our research shows that B003-2A can be used to treat ovarian cancer. The current study also laid the foundation for the development of IGF-1R antagonist.
卵巢癌是当今世界上最致命的妇科恶性肿瘤。先前的研究表明,胰岛素样生长因子-1 受体(IGF-1R)与卵巢癌的发生和发展密切相关,卵巢癌细胞内源性表达高 IGF-1R。因此,IGF-1R 可以作为治疗卵巢癌的靶点。过去,制备 IGF-1R 拮抗剂的策略是使用 IGF-1R 抗体和小分子抑制剂。在当前的研究中,我们使用一种新的方法来制备 IGF-1R 拮抗剂。我们通过抗独特型抗体策略制备了一系列 IGF-1 内成像抗独特型抗体。经过一系列的筛选和鉴定,选择了其中一种抗独特型抗体(B003-2A)进行进一步评估,结果表明 B003-2A 不仅可以抑制 IGF-1 与 IGF-1R 的结合,还可以抑制 IGF-1R 介导的信号转导。进一步的工作表明,B003-2A 可以抑制卵巢癌细胞在体内和体外的增殖。此外,本研究还表明,B003-2A 可以增强顺铂耐药卵巢癌细胞系中顺铂的敏感性。总之,我们的研究表明,B003-2A 可用于治疗卵巢癌。本研究还为 IGF-1R 拮抗剂的开发奠定了基础。