Abstract
RNA targeting the murine vascular endothelial growth factor receptor 2 (VEGFR2) gene was designed and validated for efficient and robust silencing in vitro and was delivered by polyethylenimines (PEI) in vivo to investigate the antitumor effect on non-small cell lung cancer (NSCLC) xenografts. The following dosage regimens were tested for their tumor inhibitory effect in vivo: VEGFR2 siRNA, epidermal growth factor receptor (EGFR) siRNA, VEGFR2 siRNA+EGFR siRNA, cisplatin alone and VEGFR2 siRNA+ EGFR siRNA+cisplatin. Targeted silencing of both VEGFR2 and EGFR expression by siRNA, combined with low-dose cisplatin, was found to effectively inhibit tumor growth and extend the survival time of mice bearing the NSCLC xenografts. These results suggest that combination therapy using siRNAs and chemotherapy agents might offer a novel strategy for cancer treatment in the future.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Apoptosis*
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Blotting, Western
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology*
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Carcinoma, Non-Small-Cell Lung / therapy
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Cell Proliferation
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Cisplatin / pharmacology*
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Combined Modality Therapy
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Humans
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology*
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Lung Neoplasms / therapy
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics*
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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Antineoplastic Agents
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RNA, Messenger
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RNA, Small Interfering
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EGFR protein, mouse
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ErbB Receptors
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Vascular Endothelial Growth Factor Receptor-2
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Cisplatin