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* Pages 862 - 870 ( 9 )
Background and objective: Bevacizumab (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.
Methods: Mice 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.
Results: The 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.
Conclusion: This 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.
Triple-negative breast cancer, bevacizumab, local delivery, vascular endothelial growth factor A (VEGFA), matrix metalloproteinase, I.V. therapy.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, Department of Acupuncture and Minimally Invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, Department of Traditional Chinese Medicine, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, Department of Acupuncture and Minimally Invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 100029, Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 100029, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, Department of Acupuncture and Minimally Invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029