Bevacizumab is a humanized monoclonal antibody against VEGF. It specifically binds to VEGF and blocks its binding to the corresponding receptors on the cell surface, thereby inhibiting angiogenesis[1]. Bevacizumab has high affinity for all VEGF-A isoforms and inhibits its interaction with VEGFR-1 and VEGFR-2[2]. Bevacizumab is a targeted therapy drug called an angiogenesis inhibitor that is used to study and treat many types of cancer [3].
In vitro, In vitro, low-concentration Bevacizumab (2-4 mg/ml) treated intranasal endothelial cells in HHT patients, significantly reducing the expression of VEGF after 24 hours, but it increased again after 48 hours, and exceeding 4 mg/ml would produce cytotoxic effects[4]. Bevacizumab (5-1000 ng/mL) does not cause cell death after treating U87-RFP cells for 48 hours [5].
In vivo, Bevacizumab (5 and 25 mg/kg) treated by intraperitoneal injection in mice with orthotopic glioma significantly inhibited the growth rate of tumor blood vessels and improved the survival rate[5]. Intraperitoneal administration of Bevacizumab (5 mg/kg) can prolong the survival of ovarian cancer model mice[6]. Bevacizumab (5mg/kg) showed strong anti-angiogenic activity in the treatment of osteosarcoma model mice[7].
References:
[1] Minckwitz G V , Eidtmann H , Rezai M ,et al.Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer[J].New England Journal of Medicine, 2012.
[2] Tan H, et al. 99mTc-labeled bevacizumab for detecting atherosclerotic plaque linked to plaque neovascularization and monitoring antiangiogenic effects of treatment in ApoE-/-mice. [J]Sci Rep. 2017 Jun 14;7(1):3504.
[3]Pujade-Lauraine.Bevacizumab Combined With Chemotherapy for PlatinumResistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial [J].Journal of Clinical Oncology, 2014.
[4]Haneen Sadick, Elena SchÄfer, Christel Weiss, et al. An in vitro study on the effect of bevacizumab on endothelial cell proliferation and VEGF concentration level in patients with hereditary hemorrhagic telangiectasia[J].Experimental and Therapeutic Medicine.July 5, 2022.11493.
[5]Von Baumgarten L , Brucker D , Tirniceru A ,et al. Bevacizumab Has Differential and Dose-Dependent Effects on Glioma Blood Vessels and Tumor Cells[J].Clinical Cancer Research, 2011, 17(19):6192-205.
[6]Mabuchi S , Terai Y , Morishige K ,et al.Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model.[J]Clinical Cancer Research , 2008, 14(23):7781-9.
[7]Zhao Z X , Li X , Liu W D , et al. Inhibition of Growth and Metastasis of Tumor in Nude Mice after Intraperitoneal Injection of Bevacizumab[J]. Orthopaedic Sugery. 2016.234-240.
贝伐单抗Bevacizumab是一种抗VEGF的人源化单克隆抗体,通过与VEGF特异性结合,阻断其与细胞表面相应的受体结合,进而抑制血管生成[1]。贝伐单抗对所有VEGF-A异构体具有高亲和力,并抑制其与VEGFR-1和VEGFR-2的相互作用[2]。贝伐单抗是一种靶向治疗药物,称为血管生成抑制剂,可用于研究和治疗多种类型的癌症[3]。
在体外,贝伐单抗(2-4 mg/ml)低浓度水平处理HHT患者鼻内内皮细胞,24h后显著降低了VEGF的表达,但在48h后再次升高,且超过4 mg/ml会产生细胞毒性作用[4]。贝伐单抗(5- 1000 ng/mL)处理U87-RFP细胞48h后,不会引起细胞死亡[5]。
在体内,贝伐单抗(5和25 mg/kg)通过腹腔注射治疗原位胶质瘤小鼠,显著抑制了肿瘤血管生长速率,提高了存活率[5]。贝伐单抗(5mg/kg)腹膜给药可以延长卵巢癌模型小鼠的生存期[6]。贝伐单抗(5mg/kg)治疗骨肉瘤模型小鼠,表现出较强的抗血管生成活性[7]。