Inhibition effects of gold nanoparticles on proliferation and migration in hepatic carcinoma-conditioned HUVECs |
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| Institution: | 1. Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel;2. Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway;3. University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway;4. Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway;1. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, 100193 Beijing, PR China;2. Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Hankou Road 22, Nanjing, 210093, Jiangsu, PR China;3. Jilin Agricultural University, No.2888, Xincheng Street, Changchun 130021, Jilin, PR China;4. Department of Pharmacology, School of Basic Medical Sciences, Jilin University, Changchun 130025, Jilin, PR China;5. Guang''anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, PR China |
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| Abstract: | Tumor angiogenesis is a complicated process based upon a sequence of interactions between tumor and vessel endothelial cells. Tumor conditioned medium has been widely used to stimulate endothelial cells in vitro angiogenesis. This work was aimed to investigate the effects of gold nanoparticles (GNPs) on angiogenesis in hepatic carcinoma-conditioned endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured with conditioned medium (CM) from the human hepatocarcinoma cell line HepG2 (HepG2-CM), and then treated with different concentrations of GNPs. The effects of GNPs on the viability, migration and active VEGF level of HUVECs were investigated by MTT assay, wound healing assay and transwell chamber assay, and ELISA assay, respectively. The data showed that GNPs significantly inhibited HUVECs proliferation and migration induced by HepG2-CM, and also reduced the levels of active VEGF in the co-culture system. Then, the alterations in morphology and ultrastructure of HUVECs detected by atomic force microscopy (AFM) showed that there appeared obvious pseudopodia, larger membrane particle sizes and much rougher surface in HUVECs after HepG2-CM treatment, which were all reversed after GNPs treatment. Changes in cytoskeleton of HUVECs determined by immunocytochemistry demonstrated that GNPs treatment remarkably inhibited the activation effect of HepG2-CM on HUVECs, which was associated with the disruption of actin filaments induced by GNPs. This study indicates that GNPs can significantly inhibit HepG2-CM activated endothelial cell proliferation and migration through down-regulation of VEGF activity and disruption of cell morphology, revealing the potential applications of GNPs as antiangiogenic agent for the treatment of hepatic carcinoma. |
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| Keywords: | Gold nanoparticles Tumor conditioned medium HUVECs Proliferation Migration Tumor angiogenesis |
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