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体外和体内抑制 Jagged1 抑制舌鳞状细胞癌生长。

Suppression of tongue squamous cell carcinoma growth by inhibition of Jagged1 in vitro and in vivo.

机构信息

Department of Stomatology, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, China.

出版信息

J Oral Pathol Med. 2013 Apr;42(4):322-31. doi: 10.1111/jop.12013. Epub 2012 Nov 17.

Abstract

BACKGROUND

The changes in Notch signaling are closely related to the occurrence and development of many cancers. We have investigated Notch signaling receptor and its ligand expressions in TSCC cell lines, tissues and its significance. We clarified Notch signaling pathway in TSCC and its mechanism. We regulated Notch signaling pathway of tumor cells, thereby inhibiting tumor cell proliferation and differentiation.

METHODS

We detected Jagged1 protein and mRNA expression levels in specimens (tongue cancer and adjacent tissues) from 74 patients with tongue cancer and in TSCC cell line. The Jagged1-targeted lentiviral vector RNAi system was constructed, and its suppressive effects on the proliferation and invasion of tongue carcinoma cells in in vivo and ex vivo were determined.

RESULTS

Jagged1 was expressed in tongue squamous cell cancer tissues and cell line, but there were differences in its expression. Jagged1 was knocked down and the tumor growth was inhibited accompanying cell cycle changes. Animal studies also showed that the tumor growth was inhibited.

CONCLUSIONS

Jagged1 may be involved in the differentiation and proliferation of tongue cancer. Targeting Jagged1 RNA interference lentiviral vector can effectively lower Jagged1 mRNA and protein expression levels of Tca8113 cells, thereby preventing the proliferation of TSCC cells. Jagged1 is expected to be a promising new target for curing tongue cancer. In-depth study of the interaction between Jagged1 and other molecules of Notch signaling pathway in the process of carcinogenesis has important theoretical guidance and clinical significance in revealing the mechanism of Jagged1 and its application in the therapy for tongue cancer.

摘要

背景

Notch 信号的变化与许多癌症的发生和发展密切相关。我们研究了 Notch 信号受体及其配体在 TSCC 细胞系、组织中的表达及其意义。阐明了 Notch 信号通路在 TSCC 中的作用及其机制。我们调节肿瘤细胞的 Notch 信号通路,从而抑制肿瘤细胞的增殖和分化。

方法

我们检测了 74 例舌癌患者标本(舌癌及癌旁组织)和 TSCC 细胞系中 Jagged1 蛋白和 mRNA 的表达水平。构建了靶向 Jagged1 的慢病毒载体 RNAi 系统,并在体内和体外研究了其对舌癌细胞增殖和侵袭的抑制作用。

结果

Jagged1 在舌鳞癌细胞组织和细胞系中均有表达,但表达存在差异。敲低 Jagged1 后,肿瘤生长受到抑制,细胞周期发生变化。动物研究也表明肿瘤生长受到抑制。

结论

Jagged1 可能参与舌癌的分化和增殖。靶向 Jagged1 RNA 干扰慢病毒载体可有效降低 Tca8113 细胞 Jagged1 mRNA 和蛋白的表达水平,从而抑制 TSCC 细胞的增殖。Jagged1 有望成为治疗舌癌的新靶点。深入研究 Jagged1 与 Notch 信号通路其他分子在癌变过程中的相互作用,对揭示 Jagged1 的作用机制及其在舌癌治疗中的应用具有重要的理论指导和临床意义。

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