title: 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.
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science, Health science center of Xi'an Jiaotong University, Xi'an, P. R. China, Department of Dermatology.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Dermatology, People's Hospital of Zhangdian District, Zibo City, Shandong province, P. R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, P. R. China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Pathology, Basic Medical School, Ningxia Medical University, Yinchuan, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Dermatology.
authors.forename: Nan
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Dermatology.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Dermatology.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science, Health science center of Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, USA.
authors.forename: P Andy
authors.initials: PA
authors.lastname: Li
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010766:Phosphorylation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017304:Annexin A5; D017319:Photosensitizing Agents; D050807:ets-Domain Protein Elk-1; D000622:Aminolevulinic Acid; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: MAPK; SCL-1 cell; apoptosis; photodynamic therapy; squamous carcinoma