IADR Abstract Archives
Notch Inhibitor Attenuates Cell Cycle Gene Expression in Human OSCC
Objectives: Notch inhibitor has been investigated as a candidate drug for various cancer treatments. The present study aimed to determine an influence of Notch inhibitor on human oral squamous cell carcinoma (OSCC).
Methods: The dysregulation of Notch signaling genes were determined in human OSCC biopsy using the bioinformatics analysis of public microarray database (GSE31056). Human OSCC cell line (HSC-4) were treated with Notch inhibitor (DAPT). DMSO was employed as the vehicle control. Gene expression was analyzed using real-time PCR. Cell proliferation was examined using MTT assay.
Results: Eighteen genes in Notch signaling were dysregulated in human OSCC according to microarray analysis. Notch target genes, HES2, HES4, and HEY1 were significantly upregulated while HES1 was downregulated. DAPT treatment resulted in the significant reduction of cell proliferation at day 7. Correspondingly, genes in cell cycle and DNA replication pathways were significantly reduced in DAPT treated cells, including CCND1, CCNE2, E2F2, MCM2, MCM4, MCM5, MCM8, and MCM10. Moreover, DAPT treated cells exhibited the significant reduction of MMP9 but the marked increase of TIMP1 expression. On the contrary, CD44 and CD73 mRNA levels were not changed with DAPT treatment.
Conclusions: Notch inhibitor suppresses cell proliferation and the expression of genes related to cell cycle and DNA replication. In addition, Notch inhibitor may attenuate cell invasion but not influence epithelial-mesenchymal transition.
Methods: The dysregulation of Notch signaling genes were determined in human OSCC biopsy using the bioinformatics analysis of public microarray database (GSE31056). Human OSCC cell line (HSC-4) were treated with Notch inhibitor (DAPT). DMSO was employed as the vehicle control. Gene expression was analyzed using real-time PCR. Cell proliferation was examined using MTT assay.
Results: Eighteen genes in Notch signaling were dysregulated in human OSCC according to microarray analysis. Notch target genes, HES2, HES4, and HEY1 were significantly upregulated while HES1 was downregulated. DAPT treatment resulted in the significant reduction of cell proliferation at day 7. Correspondingly, genes in cell cycle and DNA replication pathways were significantly reduced in DAPT treated cells, including CCND1, CCNE2, E2F2, MCM2, MCM4, MCM5, MCM8, and MCM10. Moreover, DAPT treated cells exhibited the significant reduction of MMP9 but the marked increase of TIMP1 expression. On the contrary, CD44 and CD73 mRNA levels were not changed with DAPT treatment.
Conclusions: Notch inhibitor suppresses cell proliferation and the expression of genes related to cell cycle and DNA replication. In addition, Notch inhibitor may attenuate cell invasion but not influence epithelial-mesenchymal transition.