Grim-19 expressed by recombinant adenovirus for esophageal neoplasmtarget therapy

Abstract

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA) are the two most common types of esophageal cancer, which is the sixth highest cause of cancer‑associated mortality and the eighth most common cancer worldwide. Gene associated with retinoid‑interferon (IFN)‑induced mortality‑19 (Grim‑19) is reported to be a cell death activator that may be used to define mechanisms involved in IFN‑β‑ and retinoic acid‑induced cell death and apoptosis in a number of tumor cell lines. The present study constructed a recombinant adenovirus expressing Grim‑19 (rAd‑Grim‑19) and investigated its therapeutic outcomes in ESCC cells and tumor‑bearing mice. Grim‑19 expression was detected in EC‑109 (ESCC) cells by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Tumor cell death and apoptosis induced by rAd‑Grim‑19 in EC‑109 cells were analyzed by flow cytometry. The inhibitory effects of rAd‑Grim‑19 on EC‑109 growth were determined by MTT assays. Furthermore, the therapeutic effects of rAd‑Grim‑19 were investigated in EC‑109‑bearing mice. The results demonstrated that Grim‑19 mRNA and protein expression was downregulated in EC‑109 esophageal carcinoma cells compared with Het‑1A normal esophageal epithelial cells. In addition, EC‑109 cells exhibited a significant reduction in tumor cell growth in the rAd‑Grim‑19 group compared with the control groups. Furthermore, rAd‑Grim‑19 increased EC‑109 cell apoptosis compared with the control group. These results indicated that rAd-Grim-19 may regulate tumor cell growth and apoptosis. Additionally, the results demonstrated that rAd‑Grim‑19 led to beneficial outcomes and prolonged the survival of esophageal tumor‑bearing mice. In conclusion, the present study demonstrated that rAd‑Grim‑19 may have potential as an antitumor agent for esophageal neoplasms and may therefore be beneficial for patients with esophageal neoplasms.