https://scholars.lib.ntu.edu.tw/handle/123456789/544383
標題: | Involvement of p38 mitogen-activated protein kinase in acquired gemcitabine-resistant human urothelial carcinoma sublines | 作者: | Kao Y.-T. Hsu W.-C. Hu H.-T. Hsu S.-H. Lin C.-S. Chiu C.-C. Lu C.-Y. Hour T.-C. YEONG-SHIAU PU Huang A.-M. |
關鍵字: | Drug resistance; Gemcitabine; p38 mitogen-activated protein kinase; Urothelial carcinoma | 公開日期: | 2014 | 出版社: | Elsevier (Singapore) Pte Ltd | 卷: | 30 | 期: | 7 | 起(迄)頁: | 323-330 | 來源出版物: | Kaohsiung Journal of Medical Sciences | 摘要: | Resistance to chemotherapeutic drugs is one of the major challenges in the treatment of cancer. A better understanding of how resistance arises and what molecular alterations correlate with resistance is the key to developing novel effective therapeutic strategies. To investigate the underlying mechanisms of gemcitabine (Gem) resistance and provide possible therapeutic options, three Gem-resistant urothelial carcinoma sublines were established (NG0.6, NG0.8, and NG1.0). These cells were cross-resistant to arabinofuranosyl cytidine and cisplatin, but sensitive to 5-fluorouracil. The resistant cells expressed lower values of [hENT1 × dCK/RRM1 × RRM2] mRNA ratio. Two adenosine triphosphate-binding cassette proteins ABCD1 as well as multidrug resistance protein 1 were elevated. Moreover, cyclin D1, cyclin-dependent kinases 2 and 4 were upregulated, whereas extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase (MAPK) activity were repressed significantly. Administration of p38 MAPK inhibitor significantly reduced the Gem sensitivity in NTUB1 cells, whereas that of an extracellular signal-regulated kinase MAPK inhibitor did not. Furthermore, the Gem-resistant sublines also exhibited higher migration ability. Forced expression of p38 MAPK impaired the cell migration activity and augmented Gem sensitivity in NG1.0 cells. Taken together, these results demonstrate that complex mechanisms were merged in acquiring Gem resistance and provide information that can be important for developing therapeutic targets for treating Gem-resistant tumors. ? 2014, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84902367825&doi=10.1016%2fj.kjms.2014.03.004&partnerID=40&md5=7e8e3df3ba55de9c2ae7cbb822b0099e https://scholars.lib.ntu.edu.tw/handle/123456789/544383 |
ISSN: | 1607-551X | DOI: | 10.1016/j.kjms.2014.03.004 | SDG/關鍵字: | 2 (2 amino 3 methoxyphenyl)chromone; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; ABC transporter; abcd1 protein; cisplatin; cyclin D1; cyclin dependent kinase 2; cyclin dependent kinase 4; cyclin dependent kinase inhibitor 1; cytarabine; cytidine; fluorouracil; gemcitabine; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase p38; multidrug resistance associated protein 1; multidrug resistance associated protein 9; multidrug resistance protein 1; reactive oxygen metabolite; unclassified drug; 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; antineoplastic antimetabolite; deoxycytidine; flavonoid; gemcitabine; imidazole derivative; mitogen activated protein kinase p38; pyridine derivative; apoptosis; article; cell cycle; chemosensitivity; controlled study; cross resistance; drug cytotoxicity; enzyme activity; gene expression; human; human cell; IC 50; protein expression; transitional cell carcinoma; upregulation; analogs and derivatives; Carcinoma, Transitional Cell; cell survival; drug effects; drug potentiation; drug resistance; drug screening; enzymology; metabolism; tumor cell line; Urinary Bladder Neoplasms; Antimetabolites, Antineoplastic; Apoptosis; Carcinoma, Transitional Cell; Cell Line, Tumor; Cell Survival; Deoxycytidine; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Flavonoids; Humans; Imidazoles; p38 Mitogen-Activated Protein Kinases; Pyridines; Urinary Bladder Neoplasms |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。