Abstract
Background
Combination of a photosensitizer, 5-aminolevulinic acid (ALA), with photodynamic therapy (PDT) has been widely used to treat skin squamous cell carcinoma (SCC). However, a portion of SCC patients do not respond well to PDT. The molecular reason for this resistance is not clear. We hypothesize that mitogen-activated phosphorylation kinase (MAPK) plays a key role in mediating SCC resistance to PDT.
Objectives
To determine whether inhibition of MAPK signaling enhances the anti-tumor effect of ALA-PDT in SCC.
Material and methods
The human squamous carcinoma cell line, SCL-1, was either untreated or treated with various combinations of ALA, PDT light source and inhibitors of MAPK signaling components.
Results
ALA-PDT treatment significantly decreased cell viability, increased the percentage of annexin-V positive cells and resulted in formation of apoptotic bodies. ALA-PDT treated cells showed increased levels of p-MEK, p-ERK1/2, p-p38, p-Elk-1, p-JNK and p-c-Jun. Addition of inhibitors for ERK1/2 (PD98059), p38 (SB203580) and JNK (SP60125) reversed the changes and led to a more dramatic decrease in SCL-1 cell viability than seen with ALA-PDT alone.
Conclusion
Inhibition of the MAPK pathway enhances the cytotoxic effect of ALA–PDT on SCL-1.
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Ge, X., Liu, J., Shi, Z. et al. Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells. Eur J Dermatol 26, 164–172 (2016). https://doi.org/10.1684/ejd.2015.2725
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DOI: https://doi.org/10.1684/ejd.2015.2725