Combination of carboplatin and photodynamic therapy with 9-hydroxypheophorbide enhances mitochondrial and endoplasmic reticulum apoptotic effect in AMC-HN-3 laryngeal cancer cells

Background: Previously, we demonstrated that the combined mode of carboplatin (CBDCA) and photodynamic therapy (PDT) based on 9-hydroxypheophorbide (9-HPbD) enhanced cytotoxicity and apoptosis on AMC-HN-3 laryngeal cancer cells. The present study aimed to investigate anti-tumor effect of the combined therapy in vivo and the potential role of reactive oxygen species (ROS) in these enhanced apoptotic pathways initiated by the combined therapy in AMC-HN-3 cells. Methods: Mitochondrial membrane potential (MMP) and intracellular Ca2+ were detected under confocal microscopy. Various apoptotic pathways were detected by western blots. In vivo study with the combined regimen was also performed on AMC-HN-3 cells-xenograft nude mice. Results: In vitro study showed that the combined treatment could decrease the level of MMP, increase intracellular Ca2+ and AIF translocation, and activate the expression of caspase-12. Mechanismly, the augmented apoptotic effect was mediated by ROS. The synergistic antitumor effect was also observed in vivo. Conclusions: The mechanism of CBDCA and 9-HPbD-PDT combination involves ROS-mediated mitochondrial and endoplasmic reticulum apoptosis pathways. This combination may be a promising treatment strategy for laryngeal cancer.