EPZ005687

Background: In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to be rising worldwide because of growing oncogenic human papillomavirus (Warts) infections within the oropharynx. EZH2 is definitely an epigenetic regulatory protein connected with tumor aggressiveness and negative survival outcomes in a number of human cancers. We aimed to look for the role of EZH2 like a potential therapeutic epigenetic target in Warts-good and bad OPSCC.

Methods: The expression of EZH2 was measured by immunohistochemistry (IHC) and droplet digital PCR (ddPCR) by 50 percent Warts-positive and a pair of Warts-negative cell lines. The cell lines were then cultured and treated and among 3 EZH2 epigenetic inhibitors (3-deazaneplanocin A, GSK-343 and EPZ005687) or DMSO (control). Following 2, 4 and seven times of treatment, cells were examined and compared by gene expression, cell survival and proliferation assays.

Results: EZH2 targeting led to greater inhibition of growth and survival in Warts-positive when compared with Warts-negative cells lines. The expression profile of genes essential in OPSCC also differed based on Warts-positivity for Ki67, CCND1, MET and PTEN/PIK3CA, but continued to be unchanged for EGFR, CDKN2A and p53.

Conclusion: Inhibition of EZH2 has anti-tumorigenic effects on OPSCC cells in culture that’s more pronounced in Warts-positive cell lines. EZH2 is really a promising epigenetic target to treat OPSCC.