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重组腺病毒介导的 Grim-19 基因治疗食管鳞癌。

Grim-19 expressed by recombinant adenovirus for esophageal neoplasm target therapy.

机构信息

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Department of Cardiothoracic Surgery, The Third People's Hospital, Yancheng, Jiangsu 224001, P.R. China.

出版信息

Mol Med Rep. 2018 May;17(5):6667-6674. doi: 10.3892/mmr.2018.8638. Epub 2018 Feb 27.

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.

摘要

食管鳞状细胞癌(ESCC)和食管腺癌(EA)是两种最常见的食管癌,是癌症相关死亡率第六高的原因,也是全球第八常见的癌症。与视黄醇干扰素(IFN)诱导的死亡 19 相关的基因(Grim-19)被报道为一种细胞死亡激活剂,可用于定义 IFN-β和维甲酸诱导的多种肿瘤细胞系中的细胞死亡和细胞凋亡机制。本研究构建了表达 Grim-19 的重组腺病毒(rAd-Grim-19),并研究了其在 ESCC 细胞和荷瘤小鼠中的治疗效果。通过逆转录-定量聚合酶链反应和 Western blot 分析检测 EC-109(ESCC)细胞中 Grim-19 的表达。通过流式细胞术分析 rAd-Grim-19 诱导 EC-109 细胞死亡和凋亡的情况。通过 MTT 测定法测定 rAd-Grim-19 对 EC-109 生长的抑制作用。此外,研究了 rAd-Grim-19 在 EC-109 荷瘤小鼠中的治疗效果。结果表明,与 Het-1A 正常食管上皮细胞相比,Grim-19 mRNA 和蛋白表达在 EC-109 食管癌细胞中下调。此外,与对照组相比,rAd-Grim-19 组 EC-109 细胞的肿瘤细胞生长明显减少。此外,rAd-Grim-19 增加了 EC-109 细胞的凋亡,与对照组相比。这些结果表明 rAd-Grim-19 可能调节肿瘤细胞的生长和凋亡。此外,研究结果表明,rAd-Grim-19 导致有益的结果并延长了食管肿瘤荷瘤小鼠的存活时间。综上所述,本研究表明 rAd-Grim-19 可能具有作为食管肿瘤的抗肿瘤剂的潜力,因此可能对食管肿瘤患者有益。

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