Pemetrexed induces G1 phase arrest and apoptosis through inhibiting Akt activation in human non small lung cancer cell line A549

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 mechanism...

Full description

Saved in:
Bibliographic Details
Published inAsian Pacific journal of cancer prevention : APJCP Vol. 16; no. 4; p. 1507
Main Authors Wu, Dong-Ming, Zhang, Peng, Xu, Guang-Chao, Tong, Ai-Ping, Zhou, Cong, Lang, Jin-Yi, Wang, Chun-Ting
Format Journal Article
LanguageEnglish
Published Thailand 2015
Subjects
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Blotting, Western
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - pathology
Cell Proliferation - drug effects
Electrophoresis, Gel, Two-Dimensional
G1 Phase - drug effects
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Pemetrexed - pharmacology
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Tumor Cells, Cultured
Online AccessGet more information

Cover

More Information
Summary: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.
ISSN:2476-762X