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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2013, Vol. 18 ›› Issue (9): 981-987.

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The anti-tumor effects and mechanism of Realgar nanoparticles on orthotopic breast cancer in mice

XI Xiao-xia1,2, FAN Lin-lan2, TIAN Yong-gang2, WANG Bei2, ZHANG Jing-ke2, CHENG Jie2, WEI Hu-lai2, WU Run1   

  1. 1College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, Gansu, China;
    2School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu, China
  • Received:2012-12-21 Revised:2013-06-26 Published:2013-09-07

Abstract: AIM: To study the anti-proliferating action of realgar nanoparticles (nano-realgar) on murine orthotopic transplanted breast carcinoma (4T1) in vitro and in vivo.METHODS: The firefly luciferase gene was transferred into murine 4T1 breast cancer cells with a lentiviral vector (4T1-Luc cells). Both MTT colorimetric assay and bioluminescence (BLM) assay was used to detect the cellular cell proliferation, the morphological observation and Annexin V and propidium iodide (Annexin V/PI) double-labeling were employed to assess the cell apoptosis in vitro. The 4T1-Luc cells were orthotopically implanted into the mammary fat pad of female BALB/c mice to establish the orthotopic transplanted model of mouse breast cancer, the tumor-bearing mice were treated with 4 mg·kg-1·d-1 and 8 mg·kg-1·d-1 nano-realgar, by gavage once a day, for 20 days, respectively, the optical in vivo imaging system was used to continuously and dynamically observe the growth, and at the end of the treatment the animals were sacrificed, and the tumor tissue was removed and weighed. The tumor tissue sections were prepared and stained with HE stain for examination of karyokinesis and necrosis in tumors, and the tumor angiogenesis was observed by CD34 immunocytochemistry.RESULTS: Both MTT and BLM assays showed that 1.56-50 μg/mL nano-realgar significantly inhibited the proliferation of 4T1-Luc cells (P<0.05), and the morphological observation and Annexin V/PI staining displayed the typical apoptotic characteristics in the cells. Nano-realgar significantly inhibited the growth of the mouse 4T1 orthotopic breast cancer in vivo at a time- and dose-dependent manner (P<0.05). The pathological and immunocytochemistry examination showed that after nano-realgar administration, the numbers of mitotic cells and microvessels in tumor tissue markedly reduced, and the extensive necrosis region could be observed at the center of the tumor tissue.CONCLUSION: Realgar nanoparticles significantly inhibits the proliferation of murine 4T1 breast cancer cells and induces to apoptosis in vitro, and plays the anti-tumor action on orthotopic transplanted breast cancer in mice via repressing neovascularization to impel necrosis of the tumor.

Key words: Realgar nanoparticle, Murine orthotopic transplanted breast cancer, Optical in vivo imaging

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