https://scholars.lib.ntu.edu.tw/handle/123456789/507733
標題: | Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells | 作者: | Cheng-Ying Shen Li-Han Chen Yu-Fen Lin LIANG-CHUAN LAI Mong-Hsun Tsai Eric Y. Chuang MONG-HSUN TSAI |
公開日期: | 2016 | 出版社: | Impact Journals LLC | 卷: | 7 | 期: | 48 | 起(迄)頁: | 79995-80007 | 來源出版物: | Oncotarget | 摘要: | Since 1984, mitomycin C (MMC) has been applied in the treatment of non-small-cell lung cancer (NSCLC). MMC-based chemotherapeutic regimens are still under consideration owing to the efficacy and low cost as compared with other second-line regimens in patients with advanced NSCLC. Hence, it is important to investigate whether MMC induces potential negative effects in NSCLC. Here, we found that the malignant lung cancer cells, CL1-2 and CL1-5, were more resistant to MMC than were the parental CL1-0 cells and pre-malignant CL1-1 cells. CL1-2 and CL1-5 cells consistently showed lower sub-G1 fractions post MMC treatment. DNA repair-related proteins were not induced more in CL1-5 than in CL1-0 cells, but the levels of endogenous and MMC-induced phosphorylated Akt (p-Akt) were higher in CL1-5 cells. Administering a p-Akt inhibitor reduced the MMC resistance, demonstrating that p-Akt is important in the MMC resistance of CL1-5 cells. Furthermore, we revealed that cell migration was enhanced by MMC but lowered by a p-Akt inhibitor in CL1-5 cells. This study suggests that in CL1-5 cells, the activity of p-Akt, rather than DNA repair mechanisms, may underlie the resistance to MMC and enhance the cells' migration abilities after MMC treatment. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84999018464&doi=10.18632%2foncotarget.13237&partnerID=40&md5=c8f3601d6cb340ce3db950126e57ce59 https://scholars.lib.ntu.edu.tw/handle/123456789/507733 |
ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.13237 | SDG/關鍵字: | 8 [4 (1 aminocyclobutyl)phenyl] 9 phenyl 1,2,4 triazolo[3,4 f][1,6]naphthyridin 3(2h) one; ATM protein; caspase 3; cell protein; checkpoint kinase 2; damage specific DNA binding protein 2; Fanconi anemia group D2 protein; mitomycin; protein kinase B; unclassified drug; xeroderma pigmentosum group C protein; mitomycin; protein kinase B; protein kinase inhibitor; Article; cell migration; cell proliferation; cell survival; cell viability; cellular distribution; CL1 0 cell line; CL1 1 cell line; CL1 2 cell line; CL1 5 cell line; concentration response; controlled study; DNA end joining repair; DNA repair; drug cytotoxicity; drug resistance; enzyme activation; enzyme activity; enzyme phosphorylation; Fanconi anemia repair; flow cytometry; G2 phase cell cycle checkpoint; human; human cell; intracellular signaling; lung cancer cell line; molecular dynamics; protein analysis; protein cleavage; protein function; time series analysis; ubiquitination; cell motion; drug effects; drug potentiation; drug resistance; lung tumor; metabolism; non small cell lung cancer; pathology; phosphorylation; signal transduction; tumor cell line; tumor invasion; upregulation; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Drug Resistance, Neoplasm; Drug Synergism; Humans; Lung Neoplasms; Mitomycin; Neoplasm Invasiveness; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; Up-Regulation |
顯示於: | 生理學科所 |
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