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Molecular Cancer
Published in: Molecular Cancer 1/2012

Open Access 01-12-2012 | Research

Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non–small-cell lung cancer xenograft models

Authors: Angela Coxon, Beth Ziegler, Stephen Kaufman, Man Xu, Hongyu Wang, Dawn Weishuhn, Joanna Schmidt, Heather Sweet, Charlie Starnes, Douglas Saffran, Anthony Polverino

Published in: Molecular Cancer | Issue 1/2012

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Abstract

Background

Non–small-cell lung cancer (NSCLC) is categorized into various histologic subtypes that play an important role in prognosis and treatment outcome. We investigated the antitumor activity of motesanib, a selective antagonist of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, platelet-derived growth factor receptor, and Kit, alone and combined with chemotherapy in five human NSCLC xenograft models (A549, Calu-6, NCI-H358, NCI-H1299, and NCI-H1650) containing diverse genetic mutations.

Results

Motesanib as a single agent dose-dependently inhibited tumor xenograft growth compared with vehicle in all five of the models (P < 0.05). When combined with cisplatin, motesanib significantly inhibited the growth of Calu-6, NCI-H358, and NCI-H1650 tumor xenografts compared with either single agent alone (P < 0.05). Similarly, the combination of motesanib plus docetaxel significantly inhibited the growth of A549 and Calu-6 tumor xenografts compared with either single agent alone (P < 0.05). In NCI-H358 and NCI-H1650 xenografts, motesanib with and without cisplatin significantly decreased tumor blood vessel area (P < 0.05 vs vehicle) as assessed by anti-CD31 staining. Motesanib alone or in combination with chemotherapy had no effect on tumor cell proliferation in vitro.

Conclusions

These data demonstrate that motesanib had antitumor activity against five different human NSCLC xenograft models containing diverse genetic mutations, and that it had enhanced activity when combined with cisplatin or docetaxel. These effects appeared to be mediated primarily by antiangiogenic mechanisms.
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Metadata
Title
Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non–small-cell lung cancer xenograft models
Authors
Angela Coxon
Beth Ziegler
Stephen Kaufman
Man Xu
Hongyu Wang
Dawn Weishuhn
Joanna Schmidt
Heather Sweet
Charlie Starnes
Douglas Saffran
Anthony Polverino
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2012
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-11-70

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