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Epidermal Growth Factor Receptor(Egfr)Dephosphorylation and Growth Inhibition by Vinorelbine in Egfr-Mutated Cell Line
Annals of Oncology 25 (Supplement 5): v75–v109, 2014 doi:10.1093/annonc/mdu436.110
Poster Session (Poster presentations categorized by each organ) P2
26
3
Hiroki Izumi1, Tadashi Igishi1, Shingo Matsumoto2, Yasuto Ueda1, Kenichi Takeda3, Hirokazu Touge1, Haruhiko Makino1, Masahiro Kodani1, S. Nirodi Chaitanya3, Eiji Shimizu1 1 Division of Medical Oncology and Molecular Respirology, Tottori University 2 National Cancer Center Hospital East 3 Michel Cancer Institution, South Alabama University
abstracts
Background: EGFR-tyrosine kinase inhibitors (TKI) often provides dramatic response to lung cancer harboring EGFR-activating mutations, but most patients eventually fail
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_5/v99/2240366 by guest on 24 October 2019
EPIDERMAL GROWTH FACTOR RECEPTOR(EGFR) DEPHOSPHORYLATION AND GROWTH INHIBITION BY VINORELBINE IN EGFR-MUTATED CELL LINE
these treatment. We have reported the efficacy of vinorelbine (VNR) and dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF) for advanced non-small cell lung cancer patients, in particular EGFR mutant lung adenocarcinoma. The aim of this research was to elucidate the mechanism of efficacy of vinorelbine and DIF to EGFR mutant lung adenocarcinoma. Methods: We used a PC9 lung adenocarcinoma cell line with EGFR- activating mutation, and evaluated whether VNR or 5FU affect the phosphorylation of EGFR using Western blotting. Then, we transfected mutated EGFR gene to 1BR3 fibroblast cell line and measured the sensitivity of VNR to 1BR3 with or without transfection of mutated EGFR. Results: In PC9 cells, VNR induced dose- and time-dependent dephosphorylation of EGFR at clinically achievable concentrations, but 5-FU did not. EGF phosphorylated EGFR and reduced the sensitivity of PC9 cells to VNR. Sodium vanadate induced sustained phosphorylation of EGFR, and also conferred resistance to VNR. The sensitivity of VNR to 1BR3 cells transfected with mutated EGFR was higher than that of the parental 1BR3 cells. Conclusions: We showed that VNR inhibits proliferation of EGFR-mutated cells through EGFR dephosphorylation.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Poster Session (Poster presentations categorized by each organ) P2
26
3
Hiroki Izumi1, Tadashi Igishi1, Shingo Matsumoto2, Yasuto Ueda1, Kenichi Takeda3, Hirokazu Touge1, Haruhiko Makino1, Masahiro Kodani1, S. Nirodi Chaitanya3, Eiji Shimizu1 1 Division of Medical Oncology and Molecular Respirology, Tottori University 2 National Cancer Center Hospital East 3 Michel Cancer Institution, South Alabama University
abstracts
Background: EGFR-tyrosine kinase inhibitors (TKI) often provides dramatic response to lung cancer harboring EGFR-activating mutations, but most patients eventually fail
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_5/v99/2240366 by guest on 24 October 2019
EPIDERMAL GROWTH FACTOR RECEPTOR(EGFR) DEPHOSPHORYLATION AND GROWTH INHIBITION BY VINORELBINE IN EGFR-MUTATED CELL LINE
these treatment. We have reported the efficacy of vinorelbine (VNR) and dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF) for advanced non-small cell lung cancer patients, in particular EGFR mutant lung adenocarcinoma. The aim of this research was to elucidate the mechanism of efficacy of vinorelbine and DIF to EGFR mutant lung adenocarcinoma. Methods: We used a PC9 lung adenocarcinoma cell line with EGFR- activating mutation, and evaluated whether VNR or 5FU affect the phosphorylation of EGFR using Western blotting. Then, we transfected mutated EGFR gene to 1BR3 fibroblast cell line and measured the sensitivity of VNR to 1BR3 with or without transfection of mutated EGFR. Results: In PC9 cells, VNR induced dose- and time-dependent dephosphorylation of EGFR at clinically achievable concentrations, but 5-FU did not. EGF phosphorylated EGFR and reduced the sensitivity of PC9 cells to VNR. Sodium vanadate induced sustained phosphorylation of EGFR, and also conferred resistance to VNR. The sensitivity of VNR to 1BR3 cells transfected with mutated EGFR was higher than that of the parental 1BR3 cells. Conclusions: We showed that VNR inhibits proliferation of EGFR-mutated cells through EGFR dephosphorylation.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].