Lapatinib inhibits receptor phosphorylation and cell growth and enhances antibody-dependent cellular cytotoxicity of EGFR- and HER2-overexpressing esophageal cancer cell lines
| Autor: | Hideki Fujii, Tetsuo Kono, Kousaku Mimura, Koji Kono, Yoshihiko Kawaguchi, Shinichiro Izawa, Rolf Kiessling, Yoshiki Mizukami, Mitsuaki Watanabe, Masayuki Inoue, Aniruddha Choudhury, Takanori Maruyama, Shugo Shiba |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Esophageal Neoplasms medicine.drug_class Cell Antineoplastic Agents Lapatinib Tyrosine-kinase inhibitor Cell Line Tumor medicine Humans Epidermal growth factor receptor Neoplasms Squamous Cell Phosphorylation skin and connective tissue diseases Cytotoxicity neoplasms Protein Kinase Inhibitors Cell Proliferation biology Cetuximab Cell Death Cell growth Antibody-Dependent Cell Cytotoxicity Genes erbB-2 digestive system diseases ErbB Receptors medicine.anatomical_structure Oncology Cancer research biology.protein Quinazolines Tyrosine kinase medicine.drug |
| Zdroj: | International journal of cancer. 129(10) |
| ISSN: | 1097-0215 |
| Popis: | Lapatinib is a dual tyrosine kinase inhibitor of the EGFR and HER2 tyrosine kinase domains. EGFR is expressed in 33.3% and HER2 in 30.3% of esophageal squamous cell carcinomas (ESCCs). To explore the potential utility of Lapatinib for therapy of ESCC patients, we evaluated the effect of Lapatinib on a panel of ESCC cell lines. EGFR and HER2 expression by the cell lines was established, and the effects of Lapatinib on inhibition of the phosphorylation of HER2, antiproliferative effect, apoptosis-inducing activity and accumulation of HER2 and EGFR on cell surface were evaluated. Additionally, the combined effect of Lapatinib together with Herceptin or Cetuximab on cell-mediated cytotoxicity was evaluated. Lapatinib inhibited HER2 phosphorylation in HER2-overexpressing, HER2 gene amplification positive ESCC cell line. Lapatinib also inhibited cell proliferation, induced apoptosis and caused the surface accumulation of HER2 and EGFR in ESCC cell lines. Addition of Lapatinib increased Herceptin-mediated antibody-dependent cell-mediated cytotoxicity by 15-25% with three ESCC target cell lines. Similarly, Cetuximab-mediated antibody-dependent cell-mediated cytotoxicity also increased by 15-30% in two ESCC cell lines on addition of Lapatinib. Cumulatively, the data indicate that Lapatinib has activity in EGFR- and/or HER2-expressing ESCC cells, and the combination therapy of Lapatinib and Cetuximab/Herceptin is a promising strategy in ESCC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text