title: COX-2 overexpression Induced by gene transfer reduces sensitivity of TE13 esophageal carcinoma cells to 5-fluorouracil and cisplatin.
abstract: Previous clinicopathological studies demonstrated that overexpression of cyclooxygenase-2 (COX-2) is associated with a poor treatment response of esophageal carcinoma. The aim of this study was to elucidate the role of COX-2 overexpression in the chemosensitivity of esophageal carcinoma cells. TE13 human esophageal squamous cell carcinoma cells were transfected with a COX-2 constitutive expression vector, and stable transfectants overexpressing COX-2 were established. COX-2 overexpression in COX-2 transfectants was confirmed with western blotting and prostaglandin-E(2) (PGE(2)) assay. Chemosensitivity testing revealed that sensitivity of COX-2 transfectants to 5-fluorouracil and cisplatin was significantly lower than in control vector-only transfectants, and that sensitivity of COX-2 transfectants was restored by the transfection of COX-2-specific siRNA. In addition, expression of antiapoptotic B-cell lymphoma-extra large (BCL-xL) and myeloid cell leukaemia-1 (MCL-1) was increased in COX-2 transfectants. These results indicate that COX-2 overexpression may reduce the chemosensitivity of esophageal carcinoma cells through up-regulation of the expression of antiapoptotic BCL-2 family proteins.
authors: Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine. 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. hfuji@koto.kpu-m.ac.jp
authors: Hiroko
authors: H
authors: Okamura
authors: Hitoshi
authors: H
authors: Fujiwara
authors: Seiji
authors: S
authors: Umehara
authors: Shinichi
authors: S
authors: Okamura
authors: Momoko
authors: M
authors: Todo
authors: Akinobu
authors: A
authors: Furutani
authors: Masayuki
authors: M
authors: Yoneda
authors: Atsushi
authors: A
authors: Shiozaki
authors: Shuhei
authors: S
authors: Komatsu
authors: Takeshi
authors: T
authors: Kubota
authors: Daisuke
authors: D
authors: Ichikawa
authors: Kazuma
authors: K
authors: Okamoto
authors: Toshiya
authors: T
authors: Ochiai
authors: Chouhei
authors: C
authors: Sakakura
authors: Yoshitaka
authors: Y
authors: Takahashi
authors: Tanihiro
authors: T
authors: Yoshimoto
authors: Eigo
authors: E
authors: Otsuji
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2; D002945:Cisplatin; D005472:Fluorouracil