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Targeting chemotherapy-induced VEGF up-regulation by VEGF antisense oligonucleotides in HNSCC cell lines

BACKGROUND: Angiogenesis is increased in various human cancers, including head and neck squamous cell carcinoma (HNSCC), and correlates with tumour progression and metastasis. Vascular endothelial growth factor (VEGF) has been shown to be a key regulator of angiogenesis. Tumour treatment with antica...

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Hauptverfasser: Riedel, Frank (VerfasserIn) , Götte, Karl (VerfasserIn) , Gößler, Ulrich (VerfasserIn) , Sadick, Haneen (VerfasserIn) , Hörmann, Karl (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 2004
In: Anticancer research
Year: 2004, Jahrgang: 24, Heft: 4, Pages: 2179-2183
ISSN:1791-7530
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://ar.iiarjournals.org/content/24/4/2179
Volltext
Verfasserangaben:Frank Riedel, Karl Götte, Ulrich Goessler, Hannen Sadick and Karl Hörmann

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520 |a BACKGROUND: Angiogenesis is increased in various human cancers, including head and neck squamous cell carcinoma (HNSCC), and correlates with tumour progression and metastasis. Vascular endothelial growth factor (VEGF) has been shown to be a key regulator of angiogenesis. Tumour treatment with anticancer agents might have an effect on the secretion of VEGF. Therefore, we determined whether certain chemotherapeutic agents stimulate VEGF secretion in HNSCC and whether VEGF antisense oligonucleotide treatment can modulate these effects in vitro. - MATERIALS AND METHODS: The effect of chemotherapeutic agents (Cisplatin, Carboplatin and 5-FU) on the production of VEGF was investigated on established human HNSCC cell lines at both mRNA and protein levels. By using a 21-mer VEGF antisense phosphorothioate oligonucleotide targeting the translation start site of human VEGF mRNA, we examined modulation of VEGF expression in cell line supernatants by capture ELISA. - RESULTS: The treatment of HNSCC cell lines with chemotherapeutic agents resulted in a significant induction of VEGF production. Carboplatin most prominently induced the release of VEGF from the tumour cells. VEGF antisense oligonucleotide treatment resulted in a significant reduction of chemotherapy-induced VEGF up-regulation compared to sense control. - CONCLUSION: Induction of VEGF secretion might contribute to the frequently observed drug resistance of HNSCC to chemotherapeutic agents. This molecular effect might be reduced by the use of VEGF antisense oligonucleotides in head and neck cancer therapy. 
650 4 |a Antineoplastic Agents 
650 4 |a Carboplatin 
650 4 |a Cell Line, Tumor 
650 4 |a Cisplatin 
650 4 |a Fluorouracil 
650 4 |a Gene Expression Regulation, Neoplastic 
650 4 |a Head and Neck Neoplasms 
650 4 |a Humans 
650 4 |a Oligonucleotides, Antisense 
650 4 |a RNA, Messenger 
650 4 |a Up-Regulation 
650 4 |a Vascular Endothelial Growth Factor A 
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