Research Papers:

Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells

Cheng-Ying Shen, Li-Han Chen, Yu-Fen Lin, Liang-Chuan Lai, Eric Y. Chuang and Mong-Hsun Tsai _

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Oncotarget. 2016; 7:79995-80007. https://doi.org/10.18632/oncotarget.13237

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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

Correspondence to:

Mong-Hsun Tsai, email: motiont@ntu.edu.tw

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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