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Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells
Abstract
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. To determine whether inhibition of MAPK signaling enhances the anti-tumor effect of ALA-PDT in SCC. 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. 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. Inhibition of the MAPK pathway enhances the cytotoxic effect of ALA-PDT on SCL-1.
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“Targeting these pro-survival signaling pathways has been shown to enhance ALA-PDT response.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [139]
In the citing paper
“In addition, several MAPK inhibitors increase PDT-induced cytotoxicity in a human squamous carcinoma cell line [139], as does the inhibition of nuclear factor erythroid 2-related factor 2 (NRF2) with an NRF2 inhibitor [140].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [139]
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References 19 · Cited by 32
Metadata
- Authors
- Ge, X., Liu, J., Shi, Z., Jing, L., Yu, N., Zhang, X., Jiao, Y., Wang, Y., & Li, P. A.
- Affiliations
- Xi'an Jiaotong University (CN)
- Ningxia Medical University (CN)
- North Carolina Central University (US)
- Venue
- European Journal of Dermatology
- Publisher
- JLE
- Published
- 2016-03
- Volume
- 26
- Issue
- 2
- Pages
- 164-172
- ISSN
- 1167-1122 (ISSN-L)
- 1952-4013
- OpenAlex
- W2327333605
- Cited by
- 32
- References
- 19
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 1
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Dermatology › Nonmelanoma Skin Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- 5-aminolevulinic acid, photodynamic therapy, cutaneous squamous cell carcinoma, MAPK signaling, apoptosis, PDT resistance, ERK1/2 inhibition, p38 MAPK inhibition, JNK inhibition, MEK inhibition, c-Jun, c-fos
- MeSH terms
- Aminolevulinic Acid, Carcinoma, Squamous Cell, Cell Survival, Humans, Phosphorylation, Photochemotherapy, Skin Neoplasms, Apoptosis, Annexin A5, Photosensitizing Agents, Drug Resistance, Neoplasm, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Cell Line, Tumor, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, ets-Domain Protein Elk-1
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- CoChat. (2026). Citation check: Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells. https://app.cochat.ai/papers/10.1684/ejd.2015.2725
- The paper
- Ge, X., Liu, J., Shi, Z., Jing, L., Yu, N., Zhang, X., Jiao, Y., Wang, Y., & Li, P. A. (2016). Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells. European Journal of Dermatology. https://doi.org/10.1684/ejd.2015.2725
