Your browser doesn't support javascript.
loading
Ribonucleotide reductase is an effective target to overcome gemcitabine resistance in gemcitabine-resistant pancreatic cancer cells with dual resistant factors.
Minami, Kentaro; Shinsato, Yoshinari; Yamamoto, Masatatsu; Takahashi, Homare; Zhang, Shaoxuan; Nishizawa, Yukihiko; Tabata, Sho; Ikeda, Ryuji; Kawahara, Kohich; Tsujikawa, Kazutake; Chijiiwa, Kazuo; Yamada, Katsushi; Akiyama, Shin-ichi; Pérez-Torras, Sandra; Pastor-Anglada, Marcal; Furukawa, Tatsuhiko; Yasuo, Takeda.
Afiliación
  • Minami K; Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima
  • Shinsato Y; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Center for the Research of Advanced Diagnosis and Therapy of Cancer, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sak
  • Yamamoto M; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Center for the Research of Advanced Diagnosis and Therapy of Cancer, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sak
  • Takahashi H; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Department of Surgical Oncology and Regulation of Organ Function, Miyazaki University School of Medicine, 5200 Kihara, Kiyotake, Miyazaki 889-1692, J
  • Zhang S; Laboratory of Molecular Genetics, Institute of Frontier Medical Sciences, Jilin University, 1163 Xinmin Street, Changchun 130021, China.
  • Nishizawa Y; Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
  • Tabata S; Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima
  • Ikeda R; Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
  • Kawahara K; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Center for the Research of Advanced Diagnosis and Therapy of Cancer, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sak
  • Tsujikawa K; Graduate School of Pharmaceutical Science, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0817, Japan.
  • Chijiiwa K; Department of Surgical Oncology and Regulation of Organ Function, Miyazaki University School of Medicine, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
  • Yamada K; Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki International University, Huis Ten Bosch Cho 2825-7
  • Akiyama S; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Clinical Research Center, National Kyushu Cancer Center, Notame, Minami-ku, Fukuoka 811-1395, Japan.
  • Pérez-Torras S; Department of Biochemistry and Molecular Biology, University of Barcelona, Institute of Biomedicine and Oncology Programme, National Biomedical Research Institute of Liver and Gastrointestinal Diseases (CIBER EHD) Diagonal 643, 08028 Barcelona, Spain.
  • Pastor-Anglada M; Department of Biochemistry and Molecular Biology, University of Barcelona, Institute of Biomedicine and Oncology Programme, National Biomedical Research Institute of Liver and Gastrointestinal Diseases (CIBER EHD) Diagonal 643, 08028 Barcelona, Spain.
  • Furukawa T; Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Center for the Research of Advanced Diagnosis and Therapy of Cancer, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sak
  • Yasuo T; Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
J Pharmacol Sci ; 127(3): 319-25, 2015 Mar.
Article en En | MEDLINE | ID: mdl-25837929
Gemcitabine is widely used for pancreatic, lung, and bladder cancer. However, drug resistance against gemcitabine is a large obstacle to effective chemotherapy. Nucleoside transporters, nucleoside and nucleotide metabolic enzymes, and efflux transporters have been reported to be involved in gemcitabine resistance. Although most of the resistant factors are supposed to be related to each other, it is unclear how one factor can affect the other one. In this study, we established gemcitabine-resistant pancreatic cancer cell lines. Gemcitabine resistance in these cells is caused by two major processes: a decrease in gemcitabine uptake and overexpression of ribonucleotide reductase large subunit (RRM1). Knockdown of RRM1, but not the overexpression of concentrative nucleoside transporter 1 (CNT1), could completely overcome the gemcitabine resistance. RRM1 knockdown in gemcitabine-resistant cells could increase the intracellular accumulation of gemcitabine by increasing the nucleoside transporter expression. Furthermore, a synergistic effect was observed between hydroxyurea, a ribonucleotide reductase (RR) inhibitor, and gemcitabine on the gemcitabine-resistant cells. Here we indicate that RR is one of the most promising targets to overcome gemcitabine resistance in gemcitabine-resistant cells with dual resistant factors.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Ribonucleótido Reductasas / Resistencia a Antineoplásicos / Desoxicitidina / Inhibidores Enzimáticos / Antimetabolitos Antineoplásicos Límite: Humans Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Japón
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Ribonucleótido Reductasas / Resistencia a Antineoplásicos / Desoxicitidina / Inhibidores Enzimáticos / Antimetabolitos Antineoplásicos Límite: Humans Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Japón