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Pemetrexed Induces G1 Phase Arrest and Apoptosis through Inhibiting Akt Activation in Human Non Small Lung Cancer Cell Line A549

  • Wu, Dong-Ming (State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University) ;
  • Zhang, Peng (Department of Radiation Oncology, Sichuan Cancer Hospital) ;
  • Xu, Guang-Chao (State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University) ;
  • Tong, Ai-Ping (State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University) ;
  • Zhou, Cong (State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University) ;
  • Lang, Jin-Yi (Department of Radiation Oncology, Sichuan Cancer Hospital) ;
  • Wang, Chun-Ting (State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University)
  • Published : 2015.03.09

Abstract

Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.

Keywords

Pemetrexed;2-DE;Akt;apoptosis;A549 non small cell lung cancer cells

Acknowledgement

Supported by : National Natural Science Foundation of China

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