Grim-19 expressed by recombinant adenovirus for esophageal neoplasmtarget therapy.

MOLECULAR MEDICINE REPORTS(2018)

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摘要
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-beta- 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.
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gene associated with retinoid-interferon-induced mortality-19,recombinant adenovirus,esophageal squamous cell carcinoma,apoptosis
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