ALA- or Ce6-PDT induced phenotypic change and suppressed migration in surviving cancer cells

Background/purpose: 5-Aminolevulinic acid mediated photodynamic therapy (ALA-PDT) has been used for the treatment of precancerous lesions and oral cancers. Compared with traditional treatment such as surgery, ALA-PDT can selectively kill cancer cells and reduce side effects. However, some cells might survive from PDT and may be directly attributable to the limited penetration of light. Therefore, it is necessary to elucidate alterations in cellular behavior and molecular mechanisms in cancer cells that have survived from PDT. Materials and methods: Human tongue squamous carcinoma cells, SCC-4 cells, and mice bearing C26 tumors were used as cancer models in vitro and in vivo. After irradiation with the LD50 (50% lethal dose) light dose, the ability of cellular migration and metastasis related gene expression were assayed. Results: Cells were rounded up and migration ability was shown to have significantly decreased under the influence of irradiation with the LD50 light dose. Gene expression related to metastasis including matrix metalloproteinases (MMPs) and chloride intracellular channel 4 (CLIC4) was also reduced. In addition, in the animal tumor model, mRNA expression of MMP9 and CLIC4 was also noticeably decreased. Conclusion: Our results indicate that PDT could reduce the expression of invasion related genes of surviving cancer cells in vitro as well as in vivo. These could be used as references for clinical PDT of oral cancer in the future.