Cancer Management and Research (Aug 2020)

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

  • Shan X,
  • Yu W,
  • Ni X,
  • Xu T,
  • Lei C,
  • Liu Z,
  • Hu X,
  • Zhang Y,
  • Cai B,
  • Wang B

Journal volume & issue
Vol. Volume 12
pp. 7475 – 7485

Abstract

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Xiuying Shan,1,* Wenjun Yu,1,* Xuejun Ni,1,* Tingting Xu,1 Chen Lei,1 Zhaoliang Liu,1 Xuefeng Hu,2 Yanding Zhang,2 Beichen Cai,1 Biao Wang1 1Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 2College of Life Sciences, Fujian Normal University, Fuzhou 350108, People’s Republic of China*These authors contributed equally to this workCorrespondence: Biao Wang Email [email protected]: 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.Keywords: angiopoietin-2, small interfering RNA, malignant melanoma, chitosan magnetic nanoparticles, apoptosis

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