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Effect of Chitosan Magnetic Nanoparticles Loaded with Ang2-siRNA Plasmids on the Growth of Melanoma Xenografts in Nude Mice

PURPOSE: Angiopoietin-2 (Ang-2) has been proven to be a potential agent for malignant cancer treatment. The aim of the current study was to investigate the inhibitory effects of chitosan magnetic nanoparticles (CMNPs) loaded with Ang-2 small interfering RNA (Ang2-siRNA) plasmids (Ang2-CMNPs) on mali...

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Detalles Bibliográficos
Autores principales: Shan, Xiuying, Yu, Wenjun, Ni, Xuejun, Xu, Tingting, Lei, Chen, Liu, Zhaoliang, Hu, Xuefeng, Zhang, Yanding, Cai, Beichen, Wang, Biao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455758/
https://www.ncbi.nlm.nih.gov/pubmed/32904466
http://dx.doi.org/10.2147/CMAR.S250479
Descripción
Sumario:PURPOSE: Angiopoietin-2 (Ang-2) has been proven to be a potential agent for malignant cancer treatment. The aim of the current study was to investigate the inhibitory effects of chitosan magnetic nanoparticles (CMNPs) loaded with Ang-2 small interfering RNA (Ang2-siRNA) plasmids (Ang2-CMNPs) on malignant melanoma. MATERIALS AND METHODS: Melanoma-bearing nude mice were treated with Ang2-CMNPs and control CMNPs. Tumor volumes in each group were recorded. Real-time fluorescence quantitative-PCR was used to measure the relative Ang-2gene expression. Angiogenesis and Ang-2 expression in tumors were measured by immunohistochemistry. Cell apoptosis in each group was measured by TUNEL staining, and the expression of Bax, Bcl-2 and cleaved caspase-3 was analyzed by immunohistochemistry. RESULTS: The progression of melanoma was significantly inhibited by Ang2-CMNP treatment. Ang2-CMNP treatment efficiently inhibited tumor growth and in-situ Ang-2 expression compared with those of the control group. Furthermore, Ang2-CMNP treatment significantly inhibited tumor angiogenesis and promoted cell apoptosis by regulating the Bax/Bcl-2 ratio and increasing cleaved caspase-3 expression in vivo. CONCLUSION: In summary, Ang2-CMNP treatment increased the regression of normal-appearing vessels in the tumor microenvironment and induced the melanoma cells apoptosis through the mitochondrial apoptotic pathway, suggesting the potential clinical use of Ang2-CMNPs in malignant melanoma treatment.