title: Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells.
abstract: 5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC-Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation (p<0.05), but there was no significant difference when the photosensitizer reached to 4.8mM. The inhibition in cell proliferation after 5-ALA-PDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle (p<0.01). Immunocytochemical observations using anti-active caspase-3 antibodies showed active caspase-3 was translocated from cytoplasm to nuclear during apoptosis. STAT3 and its downstream gene Bax and BCL-2 were changed after 5-ALA-PDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment.
authors.affiliation: Department of Dermatology, The Fourth Military Medical University, Xi'an 710032, China; Department of Dermatology, The Air Force General Hospital of PLA, Beijing 100142, China. Electronic address: Winhp2006@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China. Electronic address: xuxian1225@126.com.
authors.forename: Chengshan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing 100142, China. Electronic address: 16585620@qq.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China. Electronic address: mzsa@163.com.
authors.forename: Zhusong
authors.initials: Z
authors.lastname: Mei
authors.affiliation: Department of Radiation Oncology, Air Force General Hospital, PLA, Beijing 100142, China. Electronic address: leexinji@126.com.
authors.forename: Xinji
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing 100142, China. Electronic address: ch1031@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing 100142, China. Electronic address: liuwei5811@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents; D050796:STAT3 Transcription Factor; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid (ALA); Apoptosis; Human skins squamous cell carcinoma; Photodynamic therapy (PDT)