P-157 - Hyperthermia enhance the PDT effect via regulation of transporter expression

Abstract

Hyperthermia (HT) is a non-invasive cancer therapy and often used with other cancer therapy such as photodynamic therapy (PDT). However, mechanisms of synergistic effects among these therapies remains unclear. The 42 °C environment is a cellular mild heat stress generating O2- from mitochondrial electron transport chain. We have previously reported that the expression of ABCG2 was suppressed by increasing mitochondrial ROS. Since ABCG2 is a transporter of porphyrin, we hypothesized that synergistic effect of HT and PDT may be induced by down-regulation of ABCG2 expression via intracellular ROS increase. Rat gastric cancer cell lines were incubated at 37 or 42 °C for 1 h, then several experiments were performed. ESR signal with HT became high as compared to without HT, indicating intracellular ROS level was increased by HT. Cell viability was more decreased by HT+PDT than each monotherapy and ABCG2 expression was inhibited by HT. The enhancement of HT effect with PDT is considered to be result of down-regulation of ABCG2 expression by ROS. Thus possibly via intracellular ROS generation, and was suppressed by additional antioxidants.