Inhibition of chemotherapeutic-induced apoptosis in esophageal squamous cancer cells by the keystone periodontal pathogen, Porphyromonas gingivalis.
Date on Master's Thesis/Doctoral Dissertation
Oral Biology, MS
Scott, David A.
Committee Co-Chair (if applicable)
Lamont, Richard J.
Lamont, Richard J.
apoptosis; cisplatin; EC9076; esophageal cancer; porphyromonas gingivalis; esophageal squamous cell carcinoma; chemotherapy
Recent evidence has shown that P. gingivalis, a Gram-negative, anaerobic oral bacterium, is negatively associated with the presence and outcome of esophageal squamous cell carcinoma (ESCC). While potential underlying mechanisms are yet to be established, P. gingivalis infection is known to inhibit apoptosis in gingival epithelial cells. Therefore, we hypothesized that P. gingivalis may also inhibit of the induction of apoptosis in human ESCC cells exposed to the commonly employed anti-ESCC chemotherapeutic agent, cisplatin. The capacity of P. gingivalis, at variant multiplicities of infection, to suppress cisplatin-induced necrosis and apoptosis in EC9706 ESCC cells was established by lactate dehydrogenase (LDH) release assays, caspase-3-specific Western blots and activated caspase-3 ELISAs. LDH and activated caspase-3 levels were found to be significantly decreased by P. gingivalis for necrosis and apoptosis respectively, indicating that chemotherapeutic drug action in ESCC is rendered ineffective in presence of P. gingivalis. This study provides some of the first mechanistic insights into how esophageal infection with P. gingivalis may be associated with ESCC-related mortality.
Agrawal, Atul Kumar, "Inhibition of chemotherapeutic-induced apoptosis in esophageal squamous cancer cells by the keystone periodontal pathogen, Porphyromonas gingivalis." (2017). Electronic Theses and Dissertations. Paper 2708.