Refractory Factors in Head and Neck Cancer: ATP Binding Cassette Transporters Expressed in Head and Neck Cancer Cell Lines

  • Uematsu Takashi
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry Institute for Oral Science, Matsumoto Dental University School of Dentistry
  • Naramoto Hiroko
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry
  • Doto Ryosuke
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry
  • Uchihashi Takayuki
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry
  • Matsuura Takashi
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry
  • Usui Yohei
    Department of Orthodontics, Matsumoto Dental University School of Dentistry
  • Uematsu Setsuko
    Department of Orthodontics, Matsumoto Dental University School of Dentistry
  • Li Xianqi
    Institute for Oral Science, Matsumoto Dental University School of Dentistry
  • Takahashi Masahiro
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry
  • Yamaoka Minoru
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry
  • Furusawa Kiyofumi
    Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry Institute for Oral Science, Matsumoto Dental University School of Dentistry

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Abstract

The aim of the present study was to clarify whether ATP binding cassette transporters are refractory factors in head and neck cancer chemotherapy. For in vitro and in vivo chemotherapeutic studies, we employed a human salivary gland adenocarcinoma cell line (HSY) and a human oral squamous cell carcinoma cell line (SCCSK) with vincristine (VCR) at clinically equivalent doses. Western blot analysis, reverse transcription-polymerase chain reaction, in vivo evaluation in xenograft models inoculated with cultured carcinoma cell line and drug efflux analysis were performed. VCR-treated SCCSK and HSY cells, as well as xenografted SCCSK and HSY cells in tumor-bearing nude mice, were found to express MDR1/ABCB1 and MRP1/ ABCC1. In addition to MDR1 and MRP1 mRNA, HSY/VCR and its cloned cells expressed MRP7/ABCC10 mRNA, but SCCSK/VCR did not express MRP7. Furthermore, drug resistance to VCR and docetaxel decreased in HSY/VCR in the presence of a competitive MRP7 inhibitor, 17-beta-estradiol-(17-beta-D-glucuronide). These results indicate that MDR1 and MRP1 expression are refractory factors in head and neck cancer chemotherapy and suggest that induction of MRP7 expression is involved in drug resistance in salivary gland adenocarcinomas.

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