title: A combined modality of carboplatin and photodynamic therapy suppresses epithelial-mesenchymal transition and matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in HEp-2 human laryngeal cancer cells via ROS-mediated inhibition of MEK/ERK signalling pathway.
abstract: Photodynamic therapy (PDT) has been developed as a promising treatment modality for laryngeal cancer. 9-Hydroxypheophorbide α (9-HPbD), a novel chlorophyll-derived photosensitizer, has a longer absorption wavelength, which increases the penetration of light to malignant tissues. Carboplatin (CBDCA), a second-generation platinum derivative, also has gained more popularity for the treatment of laryngeal cancer. Our previous studies have elucidated that 9-HPbD-PDT could inhibit the migration and invasion of HEp-2 cells. The objective of this study is to investigate the change of migration and invasion of HEp-2 cells induced by a combined modality of CBDCA and 9-HPbD-PDT in vitro. A wound healing assay, cell migration assay and Matrigel invasion assay were used to evaluate the cellular migration and invasion. Reactive oxygen species (ROS) and Western blots for epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and vimentin), MMPs (MMP-2 and MMP-9) and MEK/ERK signalling pathway were performed to investigate the possible mechanisms that may be involved. We observed that CBDCA and 9-HPbD-PDT administration synergistically inhibited the migration and invasion of HEp-2 cells. Moreover, the combined modality cooperatively repressed the EMT process and down-regulated expressions of MMP-2 and MMP-9 via ROS-mediated inhibition of phosphorylation in the MEK/ERK signalling pathway. Our results suggested that the combination of CBDCA and 9-HPbD-PDT might be a promising therapeutic strategy for laryngeal cancer metastasis.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, No. 83, Fenyang Rd., Shanghai, 200031, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Mao
authors.affiliation: Department of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, No. 83, Fenyang Rd., Shanghai, 200031, China.
authors.forename: Huankang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, No. 83, Fenyang Rd., Shanghai, 200031, China.
authors.forename: Luhong
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, No. 83, Fenyang Rd., Shanghai, 200031, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, No. 83, Fenyang Rd., Shanghai, 200031, China. hepj2002@sina.com.
authors.forename: Peijie
authors.initials: P
authors.lastname: He
mesh_terms: D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: C491791:9-hydroxypheophorbide alpha; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D002734:Chlorophyll; D016190:Carboplatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: 9-Hydroxypheophorbide α; Carboplatin; Invasion; Laryngeal cancer; Migration; Photodynamic therapy