Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency.

Autor: Takeda H; Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan., Takigawa N, Ohashi K, Minami D, Kataoka I, Ichihara E, Ochi N, Tanimoto M, Kiura K
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2013 Feb 15; Vol. 319 (4), pp. 417-23. Date of Electronic Publication: 2012 Dec 27.
DOI: 10.1016/j.yexcr.2012.12.018
Abstrakt: The effectiveness of vandetanib, an agent that targets RET, VEGFR and EGFR signaling, against EGFR-mutant lung cancer cells with PTEN loss was investigated. Two EGFR mutant non-small cell lung cancer (NSCLC) cell lines, PC-9 (PTEN wild type) and NCI-H1650 (PTEN null), were used. We transfected an intact PTEN gene into H1650 cells and knocked down PTEN expression in PC-9 cells using shRNA. The effectiveness of gefitinib and vandetanib was assessed using a xenograft model. While PC-9 cells were more resistant to vandetanib than gefitinib, H1650 cells were more sensitive to vandetanib than gefitinib. Both gefitinib and vandetanib suppressed the activation of EGFR and MAPK in H1650 cells, although phosphorylated AKT levels were not affected. In an H1650 cell xenograft model, vandetanib was also more effective than gefitinib. Although PTEN-transfected H1650 cells did not show restoration of sensitivity to gefitinib in vitro, the xenograft tumors responded to gefitinib and vandetanib. Knockdown of PTEN in PC-9 cells caused resistance to gefitinib. In conclusion, vandetanib might be effective in NSCLC with EGFR mutations that lack PTEN expression. The contribution of PTEN absence to vandetanib activity in NSCLC cells harboring EGFR mutations should be further examined.
(Copyright © 2012 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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