• Curr. Pharm. Des. · Jan 2019

    Evaluation of Local Injection of Bevacizumab against Triple-Negative Breast Cancer Xenograft Tumors.

    • Xin Jiang, Qiao-Li Zhang, Tie-Gang Liu, Wei-Peng Zhao, Ming Yang, Li-Na Wang, Wei-Liang Sun, Lin Pan, Ai-Ping Luo, Jin-Chang Huang, and Xiao-Hong Gu.
    • School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
    • Curr. Pharm. Des. 2019 Jan 1; 25 (8): 862-870.

    Background And ObjectiveBevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. Therefore, the present study was to evaluate the effect of local delivery of BVZ against triple-negative breast cancer (TNBC) xenograft tumors.MethodsMice 4T1 TNBC cells were engrafted in female BALB/c mice. After the tumors reached about 5 mm (diameter), animals were treated with BVZ through the local injection from four directions around the tumors. The tumor growth, survival and potential mechanisms of action were evaluated.ResultsThe growth and microvessel density of engrafted tumors were dramatically reduced with the tumor inhibition rate of 32.8 ± 3%. No obvious side effects were observed. The expression of VEGFA, VEGF receptor (VEGFR), matrix metalloproteinase (MMP)-2, MMP-9, Delta-like ligand 4 (DLL4) and Integrin-5 was significantly reduced in TNBC tumor tissues. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-2 was significantly upregulated in xenograft tumors. Additionally, local delivery of BVZ led to the reduction of VEGFA and tumor necrosis factor (TNF)-alpha in the serum. Protein-protein interaction (PPI) analysis revealed that the proteins altered by the local delivery of BVZ were associated with angiogenesis and regulation of cell migration.ConclusionThis study provided evidence associated with local delivery of BVZ against TNBC tumors supporting the use of BVZ local injections to overcome some of the disadvantages associated with I.V. therapy with BVZ.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

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