Jia Yan, Chen Jun, Zhu He, Jia Zan-Hui, Cui Man-Hua
Department of Obstetrics and Gynecology, The Second Hospital of Jilin Universty, Changchun, Jilin 130041, P.R. China.
Oncol Rep. 2015 Nov;34(5):2296-304. doi: 10.3892/or.2015.4214. Epub 2015 Aug 20.
The presence of cancer stem cells in cervical cancer stem cells (CSCs) is important in the prevention of therapy failure and tumor recurrence. Upregulation of transcriptional regulation of redox sensing factor Nrf2 leads to the overexpression of drug efflux proteins such as ABCG2 in cancer stem cells and thus results in cancer treatment failure and cancer relapse. In the present study, we purified approximately 3.1% of cervical CSCs, which exhibited aberrant upregulation of Nrf2 in conjunction with an elevated transcriptional regulation of ABCG2, Bcl-2 and Bmi-1. Consequently, CSCs possess prolonged cell survival, infinite cell proliferation and highly resistant apoptosis. Following silencing of the function of Nrf2 the cervical CSCs became more sensitive to DNA targeting drugs and apoptosis. Our results suggested that Nrf2-mediated drug and apoptosis resistance are important in cancer therapies and tumor recurrence. Therefore, designing anticancer drugs targeting Nrf2 may be crucial to prevent CSC-mediated tumorigenesis.
宫颈癌干细胞（CSCs）中癌症干细胞的存在对于预防治疗失败和肿瘤复发至关重要。氧化还原感应因子Nrf2转录调控的上调导致癌症干细胞中药物外排蛋白如ABCG2的过度表达，从而导致癌症治疗失败和癌症复发。在本研究中，我们纯化了约3.1%的宫颈CSCs，这些细胞表现出Nrf2的异常上调，同时ABCG2、Bcl-2和Bmi-1的转录调控升高。因此，CSCs具有延长的细胞存活、无限的细胞增殖和高度抗凋亡能力。在沉默Nrf2的功能后，宫颈CSCs对靶向DNA的药物和凋亡变得更加敏感。我们的结果表明，Nrf2介导的药物和凋亡抗性在癌症治疗和肿瘤复发中很重要。因此，设计靶向Nrf2的抗癌药物对于预防CSC介导的肿瘤发生可能至关重要。
