Amprenavir inhibits pepsin‐mediated laryngeal epithelial disruption and E‐cadherin cleavage in vitro

• Published in: Laryngoscope investigative otolaryngology 2023-08, Vol.8 (4), p.953-962
• Main Authors: Samuels, Tina L., Blaine‐Sauer, Simon, Yan, Ke, Johnston, Nikki
• Format: Article
• Language: English
• Subjects: Acids; antireflux medication; Cancer; Carcinogens; Cell adhesion & migration; Drug efficacy; epithelial barrier function; extraesophageal reflux; Gastroesophageal reflux; Gene expression; Laboratories; Laryngology, Speech and Language Science; laryngopharyngeal reflux; medical therapy; Original Research
• ISSN: 2378-8038; 2378-8038
• DOI: 10.1002/lio2.1102

Background Laryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia and can promote laryngeal carcinogenesis. More than 20% of the US population suffers from LPR and there is no effective medical therapy. Pepsin is a predominant source of damage during LPR which disrupts laryngeal barrier function potentially via E‐cadherin cleavage proteolysis and downstream matrix metalloproteinase (MMP) dysregulation. Fosamprenavir (FDA‐approved HIV therapeutic and prodrug of amprenavir) is a pepsin‐inhibiting LPR therapeutic candidate shown to rescue damage in an LPR mouse model. This study aimed to examine amprenavir protection against laryngeal monolayer disruption and related E‐cadherin proteolysis and MMP dysregulation in vitro. Methods Laryngeal (TVC HPV) cells were exposed to buffered saline, pH 7.4 or pH 4 ± 1 mg/mL pepsin ± amprenavir (10–60 min). Analysis was performed by microscopy, Western blot, and real time polymerase chain reaction (qPCR). Results Amprenavir (1 μM) rescued pepsin acid‐mediated cell dissociation (p