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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 597-605

The role of the vascular endothelial growth factor/vascular endothelial growth factor receptors axis mediated angiogenesis in curcumin-loaded nanostructured lipid carriers induced human HepG2 cells apoptosis


1 Department of Pharmacy, The Second People's Hospital of Hefei, Hefei 230011, Anhui, China
2 The Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China

Correspondence Address:
Jin Chen
Department of Pharmacy, The Second People's Hospital of Hefei, Hefei 230011
China
Weidong Chen
The Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei 230012
China
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Source of Support: This research was supported by the Anhui Provincial traditional Chinese medicine scientific research project(2014zy79) and scientific research project ofsocial develop-ment plans of Hefei City in 2013 [Hefei, 2013, No 25(46)], Conflict of Interest: None


DOI: 10.4103/0973-1482.159086

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Background: Curcumin (diferuloylmethane), the active constituent of turmeric extract has potent anti-cancer properties have been demonstrated in hepatocellular carcinoma (HCC). However, its underlying molecular mechanism of therapeutic effects remains unclear. Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have crucial roles in tumor angiogenesis. Purpose: The goal of this study was to investigate the role of the VEGF/VEGFRs mediated angiogenesis during the proliferation and apoptosis of human HepG2 hepatoma cell line and the effect of curcumin-loaded nanostructured lipid carriers (Cur-NLC). Materials and Methods: The proliferation of HepG2 cells was determined by methyl thiazolyl tetrazolium after exposure to Cur-NLC and native curcumin. Apoptosis was quantified by flow cytometry with annexin V-fluorescein isothiocyanate and propidium iodide staining. Cellular internalization of Cur-NLC was observed by fluorescent microscope. The level of VEGF was detected by enzyme-linked immunosorbent assay kits. The expression of VEGFRs was quantified by Western blotting. Results: Cur-NLC was more effective in inhibiting the proliferation and enhancing the apoptosis of HepG2 cells than native curcumin. Fluorescent microscope analysis showed that HepG2 cells internalized Cur-NLC more effectively than native curcumin. Furthermore, Cur-NLC down-regulated the level of VEGF and the expression of VEGFR-2, but had a slight effect on VEGFR-1. Conclusion: These results clearly demonstrated that Cur-NLC was more effective in anti-cancer activity than the free form of curcumin. These studies demonstrate for the 1 st time that Cur-NLC exerts an antitumor effect on HepG2 cells by modulating VEGF/VEGFRs signaling pathway.


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