Synergistic inhibition of lung cancer cell invasion, tumor growth and angiogenesis using aptamer-siRNA chimeras
Journal
Biomaterials
Journal Volume
35
Journal Issue
9
Pages
2905-2914
Date Issued
2014
Author(s)
Abstract
Early metastasis is one of the major causes of mortality among patient with lung cancer. The process of tumor metastasis involves a cascade of events, including epithelial-mesenchymal transition, tumor cell migration and invasion, and angiogenesis. To specifically suppress tumor invasion and angiogenesis, two nucleolin aptamer-siRNA chimeras (aptNCL-SLUGsiR and aptNCL-NRP1siR) were used to block key signaling pathways involved in lung cancer metastasis that are pivotal to metastatic tumor cells but not to normal cells under ordinary physiologic conditions. Through nucleolin-mediated endocytosis, the aptNCL-siRNA chimeras specifically and significantly knocked down the expressions of SLUG and NRP1 in nucleolin-expressing cancer cells. Furthermore, simultaneous suppression of SLUG and NRP1 expressions by the chimeras synergistically retarded cancer cell motility and invasive ability. The synergistic effect was also observed in a xenograft mouse model, wherein the combined treatment using two chimeras suppressed tumor growth, the invasiveness, circulating tumor cell amount, and angiogenesis in tumor tissue without affecting liver and kidney functions. This study demonstrates that combined treatment of aptNCL-SLUGsiR and aptNCL-NRP1siR can synergistically suppress lung cancer cell invasion, tumor growth and angiogenesis by cancer-specific targeting combined with gene-specific silencing. ? 2013 Elsevier Ltd.
Subjects
Aptamer; Combination therapy; Lung cancer; Metastasis; SiRNA
SDGs
Other Subjects
Aptamer; Combination therapy; Lung cancer; Metastasis; siRNA; Animals; Aptamers, Nucleotide; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Gene Silencing; Human Umbilical Vein Endothelial Cells; Humans; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Invasiveness; Neovascularization, Pathologic; Neuropilin-1; Phosphoproteins; RNA, Small Interfering; RNA-Binding Proteins; Signal Transduction; Transcription Factors; Xenograft Model Antitumor Assays
Type
journal article