Abstract
The effects of class I PI3K inhibitor NVP-BKM120 on cell proliferation, cell cycle distribution, cellular apoptosis, phosphorylation of several proteins of the PI3K/AKT signaling pathway and the mRNA expression levels of HIF1-α, VEGF and MMP9 in the acquired gefitinib resistant cell line H1975 were investigated, and whether NVP-BKM120 can overcome the acquired resistance caused by the EGFR T790M mutation and the underlying mechanism were explored. MTT assay was performed to detect the effect of gefitinib, NVP-BKM120, NVP-BKM120 plus 1 μmol/L gefitinib on growth of H1975 cells. The distribution of cell cycle and apoptosis rate of H1975 cells were examined by using flow cytometry. The mRNA expression levels of tumor-related genes such as HIF1-α, VEGF and MMP9 were detected by using real-time quantitative PCR. Western blotting was used to detect the expression level of phosphorylated proteins in the PI3K/AKT signaling pathway, such as Ser473-p-AKT, Ser235/236-p-S6 and Thr70-p-4E-BP1, as well as total AKT, S6 and 4E-BP1. The results showed that the NVP-BKM120 could inhibit the growth of H1975 cells in a concentration-dependent manner, and H1975 cells were more sensitive to NVP-BKM120 than gefitinib (IC50:1.385 vs. 15.09 μmol/L resp...Continue Reading
References
May 16, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·F A ShepherdJ Berille
May 22, 2001·Molecular and Cellular Biology·E LaughnerG L Semenza
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·J R Testa, A Bellacosa
Mar 8, 2002·Cellular Signalling·Karleen M Nicholson, Neil G Anderson
Oct 11, 2002·Advances in Cancer Research·Kathleen A Martin, John Blenis
Apr 2, 2003·Journal of Cancer Research and Clinical Oncology·Branislav JeremicNebojsa Nikolic
Dec 24, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David G PfisterUNKNOWN American Society of Clinical Oncology
Mar 17, 2004·Biochimica Et Biophysica Acta·Masahito HanadaBrian A Hemmings
Mar 31, 2004·Toxicology and Applied Pharmacology·Ning GaoMohamadi A Sarkar
May 1, 2004·Science·J Guillermo PaezMatthew Meyerson
Jun 24, 2004·Seminars in Cell & Developmental Biology·Celeste J RichardsonJohn Blenis
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Mar 2, 2005·PLoS Medicine·William PaoHarold Varmus
Apr 11, 2006·Cancer·Heather A WakeleeJoan H Schiller
Apr 15, 2006·The Oncologist·David S Ettinger
Jul 19, 2006·Nature Reviews. Genetics·Jeffrey A EngelmanLewis C Cantley
Feb 7, 2007·Cancer Research·Jin Kyung RhoJae Cheol Lee
Feb 24, 2007·Nature Reviews. Cancer·Sreenath V SharmaDaniel A Haber
Apr 28, 2007·Science·Jeffrey A EngelmanPasi A Jänne
Jun 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Steven B GendreauAlison H Joly
Jul 6, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Daniel B CostaMark S Huberman
Dec 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·James BeanWilliam Pao
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cai-Hong YunMichael J Eck
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Jan 1, 2009·International Journal of Cancer. Journal International Du Cancer·Takafumi KuboShinichi Toyooka
Feb 25, 2009·British Journal of Cancer·Z TangP C Ma
Mar 17, 2009·Neuropathology and Applied Neurobiology·A IdbaihJ-Y Delattre
Apr 23, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Saadia A AzizHarriet M Kluger
Jul 9, 2010·CA: a Cancer Journal for Clinicians·Ahmedin JemalElizabeth Ward
Oct 1, 2010·Science Translational Medicine·Silvia BuonamiciMarion Dorsch
Dec 21, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Saadia A AzizHarriet M Kluger
Jun 17, 2011·BMC Cancer·Leiping WangXichun Hu