Downregulation of Notch1 induces apoptosis and inhibits cell proliferation and metastasis in laryngeal squamous cell carcinoma

作者：Dai Meng Yuan; Fang Fang; Zou You; Yi Xing; Ding Yong Jun; Chen Chen; Tao Ze Zhang; Chen Shi Ming^*

来源：Oncology Reports, 2015, 34(6): 3111-3119.

DOI：10.3892/or.2015.4274

• Notch1
• LSCC
• cell proliferation
• apoptosis
• metastasis

Notch signaling plays a key role in a wide variety of human tumors; it can be an oncogene or a tumor-suppressor gene depending on the tissue context. The functions of Notch1 in laryngeal squamous cell carcinoma (LSCC) are largely unknown. We investigated the role of Notch1 in LSCC cell growth, apoptosis and metastasis. We analyzed Notch1 expression in clinical LSCC samples using quantum dot immunohistochemistry (QD-IHC) and conventional IHC. Human laryngeal carcinoma HEp-2 cells were transfected with Notch1-specific short hairpin RNA (shRNA), and cell proliferation, apoptosis, and migration and invasion were evaluated using the cell counting assay, flow cytometry and wound healing and Transwell assays, respectively; western blotting was used to validate the expression of Notch1 target genes. Compared with normal tissues, Notch1 was upregulated in LSCC tissues; compared with LSCC tissues without metastasis, Notchl upregulation was enhanced in LSCC tissues with metastasis (P<0.05). Transfection downregulated Notchl mRNA and protein expression levels in the Notchl shRNA group. There was a significantly greater decrease in cell proliferation in the Notchl shRNA group than cell proliferation in the non-transfected (P<0.05) and negative shRNA groups (P<0.05). Furthermore, Notchl knockdown induced apoptosis in the HEp-2 cells. Additionally, the number of migrated and invasive cells in the Notchl shRNA group was decreased (P<0.05). Notchl knockdown in the HEp-2 cells greatly inhibited phosphorylated extracellular signal-related kinase (p-ERK), phosphorylated protein kinase B (p-AKT), c-Myc, BcI-2, p21, cyclin D1, cyclin-dependent kinase 4 (CDK4) and cyclin E expression levels and increased Bax expression. Altogether, our findings indicate that Notchl expression is increased in human LSCC and correlates with tumorigenesis and metastasis, while in HEp-2 cells, Notchl knockdown inhibited cell growth, induced apoptosis and inhibited migration and invasion by regulating Notchl target genes, suggesting it may be a potential therapeutic target for treating LSCC.

• 出版日期2015-12
• 单位武汉大学