Zheng Jingying, Zhao Shuhua, Yu Xiaolin, Huang Shuang, Liu Hong Yan
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Department of Gynecology and Obstetrics, The second hospital of Jilin University, Jinlin University, Changchun, 130041, China.
Theranostics. 2017 Mar 23;7(5):1373-1388. doi: 10.7150/thno.17826. eCollection 2017.
CD44 and EpCAM play crucial roles in intraperitoneal ovarian cancer development. In this study, we developed an RNA-based bispecific CD44-EpCAM aptamer that is capable of blocking CD44 and EpCAM simultaneously by fusing single CD44 and EpCAM aptamers with a double stranded RNA adaptor. With the aid of a panel of ovarian cancer cell lines, we found that bispecific CD44-EpCAM aptamer was much more effective than either single CD44 or EpCAM aptamer in the ability to inhibit cell growth and to induce apoptosis. When these aptamers were tested in intraperitoneal ovarian cancer xenograft model, bispecific CD44-EpCAM aptamer suppressed intraperitoneal tumor outgrowth much more significantly than single CD44 and EpCAM aptamer either alone or in combination. The enhanced efficacy of bispecific CD44-EpCAM aptamer is most likely to be attributed to its increased circulation time over the single aptamers. Moreover, we showed that bispecific CD44-EpCAM aptamer exhibited no toxicity to the host and was unable to trigger innate immunogenicity. Our study suggests that bispecific CD44-EpCAM aptamer may represent a promising therapeutic agent against advanced ovarian cancer.
CD44和EpCAM在腹膜内卵巢癌的发展中起着关键作用。在本研究中，我们开发了一种基于RNA的双特异性CD44-EpCAM适体，它能够通过将单个CD44和EpCAM适体与双链RNA接头融合来同时阻断CD44和EpCAM。借助一组卵巢癌细胞系，我们发现双特异性CD44-EpCAM适体在抑制细胞生长和诱导凋亡的能力方面比单个CD44或EpCAM适体有效得多。当在腹膜内卵巢癌异种移植模型中测试这些适体时，双特异性CD44-EpCAM适体比单独或联合使用的单个CD44和EpCAM适体更显著地抑制腹膜内肿瘤的生长。双特异性CD44-EpCAM适体疗效增强最可能归因于其相对于单个适体延长的循环时间。此外，我们表明双特异性CD44-EpCAM适体对宿主无毒性，并且不会引发先天性免疫原性。我们的研究表明，双特异性CD44-EpCAM适体可能是一种有前景的晚期卵巢癌治疗药物。
