Int Poster J Dent Oral Med 16 (2014), DGMKG 11. June 2014
Int Poster J Dent Oral Med 16 (2014), DGMKG (11.06.2014)
Supplement, Poster 775, Language: German/English
The influence of Paraoxonase-2 (PON-2) on resistance against radiotherapy in oral squamous cell carcinoma
Krüger, Maximilian / Moergel, Maximilian / Horke, Sven / Al-Nawas, Bilal
Background: In oral cancer apoptosis induction is a key mechanism of radiotherapy. Upregulation of antiapoptotic proteins inside the tumor leads to an advantage for survival under therapy. In vascular cells Paraoxonase-2 (PON-2) reduces overwhelming ROS-production with the potential to prevent endothelial cells to undergo mitochondrial induced apoptosis. Since irradiation typically induces elevated levels of ROS, PON-2 could also protect squamous cell carcinoma against oxidative stress. Further, some cancers (liver, oesophagus, lymphatic tissue) showed overexpression of PON-2. For today expression pattern and functional influence of PON-2 in squamous cell carcinoma of the head and neck has not been investigated.
Methods: Basal PON-2 expression was determined in vitro in four squamous cell carcinoma cell lines and in human specimen of five patients with oral cancer by western blot analysis. Induction of PON-2 protein expression after singular radiation with 7 Gray 24, 48 and 72 hours after irradiation was examined also. Simultaneously, activity of Caspase 3/7 was examined for apoptosis detection after singular irradiation and temporary PON-2 knockdown by siRNA treatment.
Results: A variable PON-2 expression pattern in vitro and in vivo was detected. Intriguingly, higher basal levels of PON-2 seem to protect cells against radiation-induced apoptosis., while singular irradiation leads to induction of PON-2. On the other hand, temporary PON-2 knockdown leads to elevated apoptosis after irradiation.
Discussion: While some tumors showed higher levels of basal PON-2 expression, other tumors upregulated PON-2 as response to therapy. Tumor cells with higher expression levels of PON-2 basal or as response to therapy may have a biological advantage to suppress irradiation induced apoptosis.
Keywords: Oral cancer, ROS, PON-2, irradiation therapy
64. Kongress der Deutschen Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie (DGMKG)
11.-14. Juni 2014