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Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo
Author(s) -
Vasvari Gergely P.,
Dyckhoff Gerhard,
Kashfi Farzaneh,
Lemke Britt,
Lohr Jennifer,
Helmke Burkhard M.,
Schirrmacher Volker,
Plinkert Peter K.,
Beckhove Philipp,
HeroldMende Christel C.
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22867
Subject(s) - thalidomide , cisplatin , hepatocyte growth factor , angiogenesis , in vivo , cancer research , pharmacology , medicine , vascular endothelial growth factor , in vitro , cell growth , immunology , biology , chemotherapy , receptor , multiple myeloma , biochemistry , vegf receptors , microbiology and biotechnology
Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro , and which tumor‐derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low‐dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro . Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor‐cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il‐8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide‐mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. © 2007 Wiley‐Liss, Inc.