Notch-1 Knockdown Suppresses Proliferation, Migration and Metastasis of Salivary Adenoid Cystic Carcinoma Cells

Background: Notch-1 promotes invasion and metastasis of cancer cells but its role in salivary adenoid cystic carcinoma (SACC) remains unelucidated. Here, we sought to investigate the effect of Notch-1 knockdown on the invasion and metastasis of SACC cells.

Methods: Stable ACC-M cells whose Notch-1 was silenced by lentiviral vectors were established. Cellular proliferation was evaluated by the MTT assays and clonogenic assays, apoptosis by flow cytometry and the migration of ACC-M cells by Transwell assays. Metastasis was evaluated by examining the number of lung nodules in Balb⁄c nu⁄nu nude mice bearing subcutaneous SACC xenografts.

Results: Our MTT assay revealed that Notch-1 knockdown significantly suppressed the proliferation of ACC-M cells compared with non-infected or scrambled control cells. Clonogenic assays further showed that Notch-1 knockdown significantly suppressed the clonogenic growth of ACC-M cells (p < 0.01 vs. controls). Our flow cytometry demonstrated that Notch-1 knockdown was associated with a significantly higher proportion of late apoptotic and necrotic cells (p < 0.01 vs. controls). Transwell assays revealed that Notch-1 knockdown markedly reduced the migratory capacity of ACC-M cells (p < 0.01 vs. controls) and xenograft studies showed that the number of metastatic nodules in the lung surface was significantly lower in nude mice bearing xenografts with Notch-1 knockdown compared to those bearing control xenografts (p < 0.01 vs. controls).

Conclusion: Notch-1 knockdown suppresses the growth and migration of SACC cells in vitro and the metastasis of SACC cells in vivo. Notch-1 may be a new candidate target in SACC.