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用短发夹RNA沉默信号转导子和转录激活子3可增强人喉鳞状细胞癌异种移植瘤在体内的放射敏感性。

Silencing STAT3 with short hairpin RNA enhances radiosensitivity of human laryngeal squamous cell carcinoma xenografts in vivo.

作者信息

Li Xiaoming, Wang Hairu, Lu Xiuying, DI Bin

机构信息

Department of Otolaryngology-Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, Hebei 050082;

出版信息

Exp Ther Med. 2010 Nov;1(6):947-953. doi: 10.3892/etm.2010.156. Epub 2010 Sep 29.

Abstract

Short hairpin RNA (shRNA) targeting signal transducer and activator of transcription 3 (STAT3) potentiate the radiosensitivity of human laryngeal squamous carcinoma cells in vitro. In the present study, we investigated the inhibitory effect of STAT3 shRNA plus radiotherapy on nude mouse laryngeal squamous cell carcinoma xenografts. The xenotransplanted tumors were treated with STAT3 shRNA, with or without radiation, following a planned scheme. The inhibition rate for tumor growth was calculated and the tumor growth curve was plotted. In addition, the expression of p-STAT3, B cell lymphoma 2 (Bcl-2), p53, vascular endothelial growth factor (VEGF) protein and intratumoral microvessel density (MVD) was determined by immunohistochemistry. Flow cytometry was used to detect the rate of cell apoptosis. The results revealed that STAT3 shRNA transfection plus radiotherapy significantly minimized tumor volume and increased the rate of tumor inhibition. p-STAT3 protein expression and intratumoral MVD were observed to be down-regulated, whereas apoptosis was increased. There was a positive correlation between the expression of p-STAT3 and Bcl-2, and also between the expression of p53 and VEGF, and MVD. These findings indicate that STAT3 shRNA potentiate the radiosensitivity of laryngeal carcinoma xenografts in vivo by regulating downstream signaling proteins in the STAT3 pathway.

摘要

靶向信号转导和转录激活因子3(STAT3)的短发夹RNA(shRNA)可增强人喉鳞状癌细胞在体外的放射敏感性。在本研究中,我们研究了STAT3 shRNA联合放疗对裸鼠喉鳞状细胞癌异种移植瘤的抑制作用。按照既定方案,对异种移植瘤进行STAT3 shRNA处理,有或无辐射。计算肿瘤生长抑制率并绘制肿瘤生长曲线。此外,通过免疫组织化学法测定p-STAT3、B细胞淋巴瘤2(Bcl-2)、p53、血管内皮生长因子(VEGF)蛋白的表达及瘤内微血管密度(MVD)。采用流式细胞术检测细胞凋亡率。结果显示,STAT3 shRNA转染联合放疗可显著减小肿瘤体积并提高肿瘤抑制率。观察到p-STAT3蛋白表达及瘤内MVD下调,而细胞凋亡增加。p-STAT3与Bcl-2的表达之间、p53与VEGF及MVD的表达之间均呈正相关。这些发现表明,STAT3 shRNA通过调节STAT3信号通路中的下游信号蛋白来增强喉癌异种移植瘤在体内的放射敏感性。

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