Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells
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Cheng-Ying Shen1,*, Li-Han Chen2,*, Yu-Fen Lin2,3,*, Liang-Chuan Lai4, Eric Y. Chuang2,5,6,7,8,9,10, Mong-Hsun Tsai1,5,6,7,11
1Institute of Biotechnology, National Taiwan University, Taipei, Taiwan
2YongLin Biomedical Engineering Center, National Taiwan University, Taipei, Taiwan
3Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
4Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan
5Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan
6Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan
7Center for Biotechnology, National Taiwan University, Taipei, Taiwan
8Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
9Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
10Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
11Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan University, Taipei, Taiwan
*These authors have contributed equally to this work
Mong-Hsun Tsai, email: firstname.lastname@example.org
Keywords: CL1-0, CL1-5, cell migration, mitomycin C, phosphorylated Akt
Received: August 17, 2016 Accepted: October 22, 2016 Published: November 09, 2016
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.
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