Dual‑regulated oncolytic adenovirus carrying ERCC1‑siRNA gene possesses potent antitumor effect on ovarian cancer cells

携带ERCC1-siRNA基因的双调控溶瘤腺病毒对卵巢癌细胞具有强大的抗肿瘤作用

阅读:13
作者:Ting Zhao #, Wei Ye #, Rui Zhang, Xiaoyan Zhu, Qin Shi, Xiaofeng Xu, Weifeng Chen, Ling Xu, Yaping Meng

Abstract

Ovarian cancer is a multifactorial and deadly disease. Despite significant advancements in ovarian cancer therapy, its incidence is on the rise and the molecular mechanisms underlying ovarian cancer invasiveness, metastasis and drug resistance remain largely elusive, resulting in poor prognosis. Oncolytic viruses armed with therapeutic transgenes of interest offer an attractive alternative to chemical drugs, which often face innate and acquired drug resistance. The present study constructed a novel oncolytic adenovirus carrying ERCC1 short interfering (si)RNA, regulated by hTERT and HIF promoters, termed Ad‑siERCC1. The findings demonstrated that this oncolytic adenovirus effectively inhibits the proliferation, migration and invasion of ovarian cancer cells. Furthermore, the downregulation of ERCC1 expression by siRNA ameliorates drug resistance to cisplatin (DDP) chemotherapy. It was found that Ad‑siERCC1 blocks the cell cycle in the G1 phase and enhances apoptosis through the PI3K/AKT‑caspase‑3 signaling pathways in SKOV3 cells. The results of the present study highlighted the critical effect of oncolytic virus Ad‑siERCC1 in inhibiting the survival of ovarian cancer cells and increasing chemotherapy sensitivity to DDP. These findings underscore the potent antitumor effect of Ad‑siERCC1 on ovarian cancers in vivo.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。