HOXC6 regulates the antitumor effects of pheophorbide a-based photodynamic therapy in multidrug-resistant oral cancer cells

Abstract

Photodynamic therapy (PDT) has been considered to be a possible candidate approach for the treatment of multidrug-resistant (MDR) cancer. To investigate the photocytotoxicity of pheophorbide a-based PDT on MDR cells, the intracellular pathways were studied using the human oral cancer FaDu cell line and its paclitaxel-selected subline FaDu-PTX. Pheophorbide a (Pa)-PDT induced significant photocytotoxicity in both FaDu and FaDu-PTX cell lines with cell apoptosis greater in FaDu cells compared to FaDu-PTX cells. We found that Hoxc6 and MDR-1 expression was strongly detected in FaDu-PTX cells compared to FaDu cells. Intriguingly, Pa-PDT effectively reduced Hoxc6 and MDR-1 expression in FaDu-PTX cells. The siRNA for HOXC6 can inhibit the intracellular MDR-1 levels in FaDu-PTX cells and induce the phototoxic effects of Pa-PDT. Furthermore, our in vivo studies showed that the Pa-PDT and HOXC6 siRNA significantly reduce the growth of FaDu-PTX xenograft tumors in C3H mice compared with control- and PTX-treated tumors. Histopathology was also used to confirm this antitumor effect. Pa-PDT may be a potential therapeutic modality for multidrug-resistant cancer, and Hoxc6, as a possible contributor to MDR, may reduce the therapeutic potential in multidrug-resistant oral malignancies.