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Published on: January 11, 2019
RUNX3 confers sensitivity to pheophorbide a-photodynamic therapy in human oral squamous cell carcinoma cell lines
Sook Moon1, Jung Yoon Bae, Hwa-Kyung Son
1Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Project, College of Dentistry, Yonsei University, Seoul, 120-752, South Korea.
Abstract:
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.
Insights
Researchers identified RUNX3 as a biomarker predicting sensitivity to pheophorbide a (Pa)-PDT in oral cancer cells. Higher RUNX3 expression correlates with increased cell death, suggesting its potential for improving photodynamic therapy efficacy.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Photodynamic therapy (PDT) is a promising cancer treatment requiring patient sensitivity screening.
- Pheophorbide a (Pa)-PDT utilizes photosensitizers to induce cancer cell death.
- Identifying biomarkers can enhance PDT effectiveness in clinical settings.
Purpose of the Study:
- To investigate a molecular biomarker for predicting sensitivity to Pa-PDT.
- To evaluate the role of RUNX3 in Pa-PDT-induced cytotoxicity in oral cells.
Main Methods:
- Utilized immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines.
- Administered Pa-PDT and assessed cell viability, reactive oxygen species generation, and apoptosis.
- Analyzed Wnt signaling-related gene expression, focusing on RUNX3.
Main Results:
- Pa-PDT reduced cell viability by over 50% and induced apoptosis in both IHOK and OSCC cells.
- Cytotoxicity of Pa-PDT was found to be proportional to RUNX3 expression levels in OSCC cell lines.
- Knockdown of RUNX3 significantly reduced Pa-PDT-induced cytotoxicity.
Conclusions:
- RUNX3 serves as a potential biomarker for determining sensitivity to Pa-PDT.
- RUNX3 expression levels can predict the efficacy of Pa-PDT in oral cancer.
- This finding may lead to novel strategies for improving PDT outcomes in oral precancerous and cancerous lesions.
