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靶向抑制S100A4的RNA干扰可抑制人喉癌Hep-2细胞的生长并促进其凋亡。

RNA interference targeting inhibition of S100A4 suppresses cell growth and promotes apoptosis in human laryngeal carcinoma Hep‑2 cells.

作者信息

Liu Jia, Fu Shuang, Xu Yingqi, Zheng Zhihong

机构信息

Laboratory Animal Center, China Medical University, Shenyang, Liaoning 110001, P.R. China.

Department of Hematology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China.

出版信息

Mol Med Rep. 2014 Sep;10(3):1389-94. doi: 10.3892/mmr.2014.2345. Epub 2014 Jun 19.

Abstract

S100A4 is a small Ca2+ binding protein that belongs to the S100 family and is involved in a number of cellular functions, including cell cycle control, proliferation, apoptosis, and has a significant role in angiogenesis and neurite extension. However, the exact function and mechanism of S100A4 in laryngeal carcinogenesis remains to be elucidated. The present study was designed to investigate the potential use of RNA interference to inhibit S100A4 expression and activation, as well as the subsequent effect on human laryngeal cancer cell growth and apoptosis. The present study demonstrated that knockdown of S100A4 decreased the proliferation and growth of the human laryngeal cancer Hep‑2 cell line. The percentages of the apoptotic cells were 4.23±1.22, 4.92±1.85 and 11.70±4.02% in the control, negative control and S100A4 short hairpin RNA (shRNA) groups, respectively, indicating significant differences among the different groups. The S100A4‑mediated induction of apoptosis was demonstrated to be associated with the activation of caspase‑3, caspase‑8 and caspase‑9. Intratumoral injection of S100A4‑shRNA inhibited tumor growth in nude mice. Thus, knockdown of S100A4 inhibited the progression of laryngeal squamous carcinoma, decreased proliferation and promoted apoptosis. S100A4 is a potential candidate for therapeutic targeting of laryngeal carcinoma cells.

摘要

S100A4是一种小的钙离子结合蛋白,属于S100家族,参与多种细胞功能,包括细胞周期调控、增殖、凋亡,并且在血管生成和神经突延伸中发挥重要作用。然而,S100A4在喉癌发生中的具体功能和机制仍有待阐明。本研究旨在探讨RNA干扰抑制S100A4表达和激活的潜在用途,以及对人喉癌细胞生长和凋亡的后续影响。本研究表明,敲低S100A4可降低人喉癌Hep-2细胞系的增殖和生长。对照组、阴性对照组和S100A4短发夹RNA(shRNA)组的凋亡细胞百分比分别为4.23±1.22%、4.92±1.85%和11.70±4.02%,表明不同组之间存在显著差异。S100A4介导的凋亡诱导与caspase-3、caspase-8和caspase-9的激活有关。瘤内注射S100A4-shRNA可抑制裸鼠肿瘤生长。因此,敲低S100A4可抑制喉鳞状细胞癌的进展,降低增殖并促进凋亡。S100A4是喉癌细胞治疗靶点的潜在候选者。

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