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为探索BDNF/TrkB途径是否可能成为治疗MM的潜在靶点、抗脑源性神经营养因子(BDNF)单克隆抗体能否阻碍疾病的发展,用骨髓瘤异体移植的动物模型评估在体内BDNF单克隆抗体的抗肿瘤活性。选择糖尿病抵抗/重症联合免疫缺陷(NOD/SCID)小鼠,皮下注射人骨髓瘤细胞系RPMI8226细胞建立异体移植动物模型。抗体以20μg/只的剂量于接种肿瘤细胞后第1、2、3天腹腔内注射或者以100μg/只的剂量于检测到瘤体后每周1次腹腔内注射。采用组织学方法检测瘤细胞的形态特征,以免疫组织化学染色法分析瘤组织的微血管密度,应用3H-TdR掺入法和Matrigel网状结构形成实验分别检测BDNF单克隆抗体对RPMI8226细胞体外增殖和PRMI8226细胞诱导的内皮细胞血管新生的影响。结果表明:在建立的骨髓瘤细胞异体移植动物模型内,多次注射BDNF单克隆抗体可缩小肿瘤体积,降低瘤组织微血管密度,延长无病生存期和生存时间,而且BDNF单克隆抗体可显著抑制体外RPMI8226细胞的增殖和诱导内皮细胞血管新生,而相应的对照抗体却无此效应。结论:BDNF单克隆抗体可抑制动物模型中皮下浆细胞瘤的生长和血管新生。
To explore whether the BDNF / TrkB pathway may be a potential target for the treatment of MM, whether anti-brain derived neurotrophic factor (BDNF) monoclonal antibodies can hinder the development of the disease, an animal model of myeloma xenograft was used to assess the in vivo BDNF monoclonal Antitumor activity of the antibody. We selected diabetic mice / severe combined immunodeficiency (NOD / SCID) mice and subcutaneously injected human myeloma cell line RPMI8226 cells to establish animal models of allograft. Antibody was intraperitoneally injected at 1, 2, 3 days after tumor cell inoculation at a dose of 20 μg / mouse or intraperitoneally once a week after the tumor was detected at a dose of 100 μg / mouse. The morphological features of tumor cells were detected by histological method. The microvessel density of tumor tissue was analyzed by immunohistochemical staining. 3H-TdR incorporation and Matrigel reticular formation were used to detect the proliferation and proliferation of RPMI8226 cells in vitro Effect of PRMI8226 Cells on Endothelial Angiogenesis. The results showed that multiple injections of BDNF monoclonal antibody reduced the tumor volume, reduced the microvessel density of the tumor tissue, prolonged disease-free survival and survival time in established animal models of myeloma cell xenotransplantation. Moreover, the monoclonal antibody against BDNF significantly inhibited Proliferation of RPMI8226 cells in vitro and induction of endothelial angiogenesis, whereas the corresponding control antibody did not. CONCLUSION: BDNF monoclonal antibody inhibits the growth and angiogenesis of subepithelial neoplasia in animal models.