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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / antagonists & inhibitors*
  • Calcium-Binding Proteins / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Culture Techniques
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Cell Transformation, Neoplastic / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Gene Transfer Techniques
  • Genetic Vectors / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Jagged-1 Protein
  • Lentivirus / genetics
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Serrate-Jagged Proteins
  • Signal Transduction / genetics
  • Skin Neoplasms / pathology
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / pathology*

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Membrane Proteins
  • RNA, Small Interfering
  • Serrate-Jagged Proteins