The present study aimed to investigate the ability of a novel form of the anti-angiogenic molecular antibody drug to induce Myeloma cell death after cultivation upon endothelial feeder cells. Bevacizumab-loaded chitosan (BCS) nanoparticles (NPs) were prepared by the ionic gelation method. Human U266 cell line and human umbilical vein endothelial cells were co-cultured for 72 h and treated with BCS nanoparticles (10μM) to study their impact on inhibition of cell growth and induction of apoptosis. Death assessments, P53 pro-apoptotic marker expression and the VEGF level were investigated by flow-cytometric analyses of the Annexin V, immunocytochemistry and ELISA, respectively. The endothelial monolayer co-culture showed protection of myeloma cells from apoptosis when exposed to NPs or without any treatment. In present of bevacizumab, the VEGF factor was effectively suppressed, and the p53 expression was significantly increased in bevacizumab-treated myeloma cells co-cultured with HUVECs, compared to other groups. BCS was capable of disturbing the effective interconnections of myeloma cells and HUVECs as supportive cells. Disruptions of tumor cells' connections with their microenvironment and blocking their possible supportive pathways might be a potential strategy to eradicate tumor cells and finally cure such types of cancer.

本研究旨在研究一种新型抗血管生成分子抗体药物在内皮饲养细胞上培养后诱导骨髓瘤细胞死亡的能力。通过离子凝胶法制备负载贝伐单抗的壳聚糖 (BCS) 纳米粒子 (NPs)。将人U266细胞系和人脐静脉内皮细胞共培养72小时，并用BCS纳米颗粒（10μM）处理，以研究它们对抑制细胞生长和诱导细胞凋亡的影响。分别通过膜联蛋白 V、免疫细胞化学和 ELISA 的流式细胞分析来研究死亡评估、P53 促凋亡标记物表达和 VEGF 水平。当暴露于 NPs 或未经任何治疗时，内皮单层共培养物显示出保护骨髓瘤细胞免于凋亡。在贝伐单抗的存在下，与其他组相比，与 HUVEC 共培养的贝伐单抗处理的骨髓瘤细胞中，VEGF 因子被有效抑制，p53 表达显着增加。BCS 能够干扰骨髓瘤细胞和 HUVEC 作为支持细胞的有效互连。破坏肿瘤细胞与其微环境的联系并阻断其可能的支持途径可能是根除肿瘤细胞并最终治愈此类癌症的潜在策略。