title: Preclinical validation of talaporfin sodium-mediated photodynamic therapy for esophageal squamous cell carcinoma.
abstract: Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.
authors.affiliation: Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohashi
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kikuchi
authors.affiliation: Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Tsurumaki
authors.affiliation: Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiroi
authors.initials: H
authors.lastname: Kasai
authors.affiliation: Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horimatsu
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Muto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005453:Fluorescence; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D011166:Porphyrins; D017382:Reactive Oxygen Species; C053434:Talaporfin
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