4.4 Article

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

期刊

JOURNAL OF ORAL PATHOLOGY & MEDICINE
卷 42, 期 4, 页码 322-331

出版社

WILEY-BLACKWELL
DOI: 10.1111/jop.12013

关键词

Jagged1; lentiviral vector; Notch; RNA interference; tongue squamous cell carcinoma

资金

  1. National Natural Science Foundation of China [30772442]
  2. Postdoctoral Science Foundation of China [2012M511877]
  3. Scientific Projects of Zhongshan City

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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.

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