Wang Tian, Li Yan, Tuerhanjiang Abidan, Wang Wenwen, Wu Zhangying, Yuan Ming, Maitituoheti Mayinuer, Wang Shixuan
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Oncol Lett. 2014 Apr;7(4):1102-1108. doi: 10.3892/ol.2014.1816. Epub 2014 Jan 21.
Cisplatin is regularly used in the treatment of ovarian cancer. However, the drug only provides a modest survival advantage, primarily due to chemoresistance and the upregulation of antiapoptotic machineries in ovarian cancer cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in ovarian cancer cells may improve the therapeutic outcomes. Twist basic helix-loop-helix transcription factor 2 (Twist2) is a novel zinc finger transcription factor that has been indicated to be an important inducer of epithelial-mesenchymal transition, which has been shown to be involved in various phases of tumorigenicity and progression. However, whether Twist2 suppression increases the chemosensitivity of ovarian cancer cells to chemotherapeutic agents remains unclear. In the present study, Twist2 expression was found to differ between human ovarian cisplatin-sensitive cancer cell line, OV2008, and the resistant variant, C13K cells. Twist2 plasmids or RNA interference were then utilized to alter Twist2 expression in OV2008 or C13K cells, respectively, to further assess apoptosis, cell viability and cell growth, as well as a possible mechanism. The results of the present study indicated that Twist2 plays a crucial role in the chemoresistance of ovarian cancer. In addition, the downregulation of Twist2 expression may facilitate apoptosis and recover the sensitivity of chemoresistant ovarian cancer through the protein kinase B/glycogen synthase kinase-3β pathway. Therefore, Twist2 depletion may be a promising approach to ovarian cancer therapy.
顺铂常用于治疗卵巢癌。然而,该药物仅能带来适度的生存优势,主要原因是化疗耐药性以及卵巢癌细胞中抗凋亡机制的上调。因此,针对卵巢癌细胞中导致顺铂耐药的机制进行靶向治疗可能会改善治疗效果。Twist碱性螺旋-环-螺旋转录因子2(Twist2)是一种新型锌指转录因子,已被证明是上皮-间质转化的重要诱导因子,而上皮-间质转化已被证实参与肿瘤发生和进展的各个阶段。然而,Twist2的抑制是否会增加卵巢癌细胞对化疗药物的化疗敏感性仍不清楚。在本研究中,发现人类卵巢顺铂敏感癌细胞系OV2008和耐药变体C13K细胞之间的Twist2表达存在差异。然后分别利用Twist2质粒或RNA干扰来改变OV2008或C13K细胞中的Twist2表达,以进一步评估细胞凋亡、细胞活力和细胞生长情况以及可能的机制。本研究结果表明,Twist2在卵巢癌的化疗耐药中起关键作用。此外,Twist2表达的下调可能通过蛋白激酶B/糖原合酶激酶-3β途径促进细胞凋亡并恢复化疗耐药卵巢癌的敏感性。因此,Twist2的缺失可能是一种有前景的卵巢癌治疗方法。