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Ribonucleotide reductase is an effective target to overcome gemcitabine resistance in gemcitabine-resistant pancreatic cancer cells with dual resistant factors
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نویسنده
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minami k. ,shinsato y. ,yamamoto m. ,takahashi h. ,zhang s. ,nishizawa y. ,tabata s. ,ikeda r. ,kawahara k. ,tsujikawa k. ,chijiiwa k. ,yamada k. ,akiyama s.-i. ,pérez-torras s. ,pastor-anglada m. ,furukawa t. ,yasuo t.
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منبع
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journal of pharmacological sciences - 2015 - دوره : 127 - شماره : 3 - صفحه:319 -325
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چکیده
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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 thegemcitabine-resistant cells.hereweindicate that rrisoneofthe most promising targetstoovercome gemcitabine resistance in gemcitabine-resistant cells with dual resistant factors. © 2015 japanese pharmacological society. production and hosting by elsevier b.v.
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کلیدواژه
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Anticancer agent resistance; Gemcitabine; Nucleoside transporter; Pancreatic cancer; Ribonucleotide reductase
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آدرس
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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,890-8544, Japan, 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 sakuragaoka,kagoshima,890-8544, Japan, 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 sakuragaoka,kagoshima,890-8544, Japan, 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, Japan, laboratory of molecular genetics,institute of frontier medical sciences,jilin university,1163 xinmin street,changchun,130021, China, 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 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,890-8544,japan,institute for advanced biosciences,keio university,mizukami 246-2,kakuganji,tsuruoka,yamagata,997-0052, Japan, 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,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 sakuragaoka,kagoshima,890-8544, Japan, graduate school of pharmaceutical science,osaka university,yamada-oka 1-6,suita,osaka,565-0817, Japan, department of surgical oncology and regulation of organ function,miyazaki university,school of medicine,5200 kihara,kiyotake,miyazaki,889-1692, Japan, 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,sasebo,nagasaki,859-3298, Japan, 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, department of biochemistry and molecular biology,university of barcelona,institute of biomedicine and oncology programme,barcelona,08028, Spain, department of biochemistry and molecular biology,university of barcelona,institute of biomedicine and oncology programme,barcelona,08028, Spain, 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 sakuragaoka,kagoshima,890-8544, Japan, department of clinical pharmacy and pharmacology,graduate school of medical and dental sciences,kagoshima university,8-35-1 sakuragaoka,kagoshima,890-8544, Japan
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Authors
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