Photodynamic therapy (
PDT) with
photosensitizer is one of the promising modalities for
cancer treatment. For clinical use of
PDT, screening process should be preceded to enhance sensitivity to
PDT. Thus, we investigated a molecular
biomarker to determine the sensitivity to
pheophorbide a (Pa)-
PDT in immortalized human oral keratinocytes (IHOK) and
oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-
PDT, cell viability was reduced by more than 50%, and
reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in
PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-
PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related
transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to
PDT. We found that the cytotoxicity by Pa-
PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-
PDT, suggesting that RUNX3 might be a
biomarker to determine sensitivity to Pa-
PDT. This was the first study to find a new target molecule that enhances Pa-
PDT effects in IHOK and OSCC cell lines. Hence, the development of a
PDT-dependent
biomarker could provide a novel approach to improve the effects of
PDT on oral precancerous and cancerous lesions.