title: Downregulation of midkine induces cisplatin resistance in human oral             squamous cell carcinoma.
abstract: The presence of drug-resistant cancer cells has been associated with poor             clinical outcomes. Cisplatin is one of the most effective chemotherapeutic agents             commonly used for several malignancies including oral squamous cell carcinoma             (OSCC). Although cisplatin resistance is a major obstacle in cancer treatment,             mechanisms by which it develops are not well understood. Midkine (MK), a heparin-binding             growth factor, has various cancer-related functions. In this study, we investigated             whether MK is involved in cisplatin resistance in OSCC. We demonstrated that the             Sa-3R cell line, which is OSCC cisplatin-resistant, exhibited lower MK expression             with slow growth compared with its parent, Sa-3 cells. In Sa-3 cells, downregulation             of MK expression significantly reduced cisplatin sensitivity, cell growth, and             the expression of cyclin D1 and cyclin E1. MK knockdown suppressed cellular cisplatin             accumulation via induction of ATP-binding cassette efflux transporters. These             data suggest that MK may play important roles in cisplatin resistance in OSCC             by modulating both cell growth and intracellular cisplatin accumulation.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School                     of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ota
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Ota
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinriki
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Takanao
authors.initials: T
authors.lastname: Sueyoshi
authors.forename: Ken
authors.initials: K
authors.lastname: Nakatani
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hiraishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Fujita
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Shinohara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000078792:Midkine; D009062:Mouth Neoplasms / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D000078792:Midkine; D002945:Cisplatin