A novel 450-nm laser-mediated sinoporphyrin sodium-based photodynamic therapy induces autophagic cell death in gastric cancer through regulation of the ROS/PI3K/Akt/mTOR signaling pathway

Background: Photodynamic therapy (PDT) has become an ideal and promising therapeutic method for fighting Cancer, but its common application in clinical practice is prevented by the limitations of expensive devices in LIGHT sources and phototoxicity in photosensitizers. The aim of this study was to explore the antitumor efficiency of the novel 450-nm blue laser (BL) combined with sinoporphyrin sodium (DVDMS)-mediated PDT against human gastric Cancer (GC) in vitro and in vivo, focusing on Autophagy pathway.

Methods: Cell viability was detected by Cell Counting Kit-8 and colony formation assays in HGC27, MGC803, AGS, and GES-1 cells. Cell Apoptosis was measured by flow cytometry and western blotting. The production of Reactive Oxygen Species (ROS) was measured by fluorescence microscopy and flow cytometry. Autophagy was determined by transmission electron microscopy and western blotting. The antitumor effect of BL-PDT in vivo was detected by a subcutaneous tumor model in nude mice.

Results: The novel 450-nm laser-mediated DVDMS-based PDT caused remarkable growth inhibition and Apoptosis induction in GC cells in vitro by the production of excessive ROS. Autophagy flux was induced by BL-PDT in GC cells, as determined by LC3 conversion assay, LC3 turnover assay, and mRFP-GFP-LC3 puncta assay. Furthermore, Autophagy induction was demonstrated to positively contribute to BL-PDT-induced apoptotic effects on GC cells. Mechanically, ROS/PI3K/Akt/mTOR pathway was identified to involve in the regulation of BL-PDT-induced Autophagy as determined by transcriptomic analysis and functional studies. Consistently, xenograft studies confirmed the significant antitumor effect of BL-PDT and its favorable safety in vivo.

Conclusions: The novel 450-nm laser-mediated DVDMS-based PDT may be a safe and effective approach against GC. Our results thus provide compelling evidence for the therapeutic application of BL-PDT in human GC.

Apoptosis; Autophagy; GC; PDT; ROS.