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The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines

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Authors
Kim, Jin Won; Kim, Hwang-Phill; Im, Seock-Ah; Kang, Soyeong; Hur, Hyung Seok; Yoon, Young-Kwang; Oh, Do-Youn; Kim, Jee Hyun; Lee, Dong Soon; Kim, Tae-You; Bang, Yung-Jue
Issue Date
2008-09-09
Publisher
Elsevier
Citation
Cancer Lett. 2008 Dec 18;272(2):296-306. Epub 2008 Sep 6.
Keywords
Antineoplastic Agents/*pharmacologyApoptosis/drug effectsBlotting, WesternCell Division/*drug effectsCell Line, TumorHumansIn Situ Hybridization, FluorescencePhosphorylationProtein Kinase Inhibitors/*pharmacologyQuinazolines/*pharmacologyReceptor, Epidermal Growth Factor/*antagonists & inhibitorsReceptor, erbB-2/*antagonists & inhibitors
Abstract
HER2 overexpression is observed in 5-25% of gastric cancers. Lapatinib is a dual inhibitor of the epidermal growth factor receptor and HER2 tyrosine kinase. We examined the antitumor effect of lapatinib in gastric cancer cell lines. Lapatinib induced selective and potent growth inhibition in two HER2-amplified gastric cancer cell lines (SNU-216 and NCI-N87). Lapatinib inhibited the phosphorylation of HER2, EGFR and downstream signaling proteins, resulting in G1 arrest in both cell lines with down-regulation of cMyc and induction of p27kip1. Lapatinib also induced apoptosis in NCI-N87 which has high HER2 amplification ratio. Lapatinib combined with 5-fluorouracil, cisplatin, oxaliplatin or paclitaxel showed an additive or synergistic effect. These results provide a rationale for the future clinical trials of lapatinib combined with cytotoxic drugs in the treatment of HER2-positive gastric cancer.
ISSN
1872-7980 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18774637

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T54-4TCPN7R-2-C&_cdi=4992&_user=168665&_orig=search&_coverDate=12%2F18%2F2008&_sk=997279997&view=c&wchp=dGLbVzz-zSkWA&md5=c26709ba503085cbe65c71724b43a3f8&ie=/sdarticle.pdf

http://hdl.handle.net/10371/46305
DOI
https://doi.org/10.1016/j.canlet.2008.07.018
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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