EXPLORING COMPARATIVELY THE CYTOTOXICITY OF MILLEDAND 3D-PRINTED PMMA-BASED RESINS TO ORAL SQUAMOUSCANCER CELLS – WHAT SIGNALS COULD THE AKT/MTORPATHWAY SEND US THROUGH ITS DOWNSTREAM EFFECTORGSK-3?

Dan S. Enasescu, Bianca Voicu-Balasea, Florentina Rus-Hrincu, Radu Radulescu, Alexandra Popa, Mihai Radu Moisa, Bogdan-Ioan Coculescu, Marina Melescanu Imre, Silviu M. Pituru, Alexandra Ripszky

Romanian Journal of Oral Rehabilitation

Abstract

Aim of the study In this study, we aimed to provide more experimental data regarding the possible cytotoxic
effects of two types of PMMA-based resin samples (CAD/CAM milled and 3D-printed) on human oral squamous
carcinoma cells. Furthermore, we have also explored the possible alterations of the Akt pathway and its
downstream target, apoptosis, in the exposed cells to the two types of resin samples. During the last few years,
PMMA-based materials have been extensively explored and modified in order to obtain the desired and ideal
properties for dentistry applications. However, there are certain unsolved issues regarding the PMMA-based
obturators, including possible cytotoxicity due to the residual monomers. As far as we know there are no studies
targeting the Akt/mTOR signalling pathway in the human oral squamous carcinoma cells, exposed to PMMAbased resins used for maxillary obturator manufacturing. Material and methods 25 samples of PMMA- based
resin were printed with SHERAeco-print 30 resin using Digital Light Processing (DLP) technique. The resin was
layered with a thickness of 50 μm. The Human Oral Squamous Carcinoma Cell Line (OECM-1 cell line) were
cultured in a humidified atmosphere at 37 degrees Celsius and 5% carbon dioxide. Results Our results showed
that the exposure of OECM-1cells to two types of PMMA-based dental resins induced cytotoxic effects, probably
via a residual monomer-induced overproduction of ROS, triggering the decrement of cell viability. Furthermore,
exposure to the PMMA-based resins disturbed the Akt/mTOR/GSK-3 signaling pathway compared to the
unexposed control cells. Moreover, our results might suggest that the noticed decreased cell viability should be
attributed to the activation of apoptosis, via a detouring signaling pathway, possibly orchestrated by Bcl-2.
Conclusion Within the limitations of the present in vitro study, our results surprisingly revealed that exposure of
OECM-1cells to the two types of PMMA-based dental resins (MA-CAD/CAM and MA-3D printed) induced
cytotoxic effects and reduced cell viability probably by activation of apoptosis. Due to the experimental limitations
of the present study, our data must be considered preliminary.

Keywords: PMMA-based, dental resin, Akt/mTor, GSK3, apoptosis, maxillary obturator