Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells.
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.
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
Cheng-Ying
CY
Shen
YongLin Biomedical Engineering Center, National Taiwan University, Taipei, Taiwan.
Li-Han
LH
Chen
YongLin Biomedical Engineering Center, National Taiwan University, Taipei, Taiwan.|Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Yu-Fen
YF
Lin
Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
Liang-Chuan
LC
Lai
YongLin Biomedical Engineering Center, National Taiwan University, Taipei, Taiwan.|Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan.|Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei, Taiwan.|Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.|Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Eric Y
EY
Chuang
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.|Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan.|Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei, Taiwan.|Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan University, Taipei, Taiwan.
Mong-Hsun
MH
Tsai
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016685:Mitomycin / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D047428:Protein Kinase Inhibitors; D016685:Mitomycin; D051057:Proto-Oncogene Proteins c-akt
CL1-0; CL1-5; cell migration; mitomycin C; phosphorylated Akt