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

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 G 1 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.