寻找针对肿瘤血管生成的有效策略仍然是癌症研究的一个关键目标。我们提出了一种利用交变电场抑制肿瘤血管生成并增强贝伐珠单抗治疗效果的开创性方法。鸡绒毛尿囊膜、细胞活力和体外内皮管形成实验表明，频率为1000kHz、电场强度为0.6V/cm的电场可抑制血管内皮细胞的生长，并抑制肿瘤诱导的血管生成。在动物 U87MG 神经胶质瘤模型中，1000kHz 电场抑制肿瘤血管生成并抑制肿瘤生长。 3D 血管分析表明，对照组的肿瘤血管系统是一个坚固的、交织的网络。然而，电场将其转变为细长、平行的毛细管，并且严格垂直于电场方向。这种结构转变伴随着血管内皮细胞的凋亡和肿瘤血管数量的显着减少。此外，我们发现电场的抗血管生成和肿瘤抑制作用与贝伐单抗具有协同作用。电场的抗血管生成机制包括破坏内皮细胞分裂期间的纺锤体形成以及下调环境血管生成相关细胞因子，例如白介素-6、CXCL-1、2、3、5和8以及基质金属蛋白酶。总之，我们的研究结果证明了交流电场 (AEF) 作为阻碍血管生成和抑制癌症生长的治疗方式的潜力。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

The search for effective strategies to target tumour angiogenesis remains a critical goal of cancer research. We present a pioneering approach using alternating electric fields to inhibit tumour angiogenesis and enhance the therapeutic efficacy of bevacizumab. Chicken chorioallantoic membrane, cell viability and in vitro endothelial tube formation assays revealed that electric fields with a frequency of 1000 kHz and an electric intensity of 0.6 V/cm inhibited the growth of vascular endothelial cells and suppressed tumour-induced angiogenesis. In an animal U87MG glioma model, 1000 kHz electric fields inhibited tumour angiogenesis and suppressed tumour growth. As demonstrated by 3D vessel analysis, tumour vasculature in the control group was a stout, interwoven network. However, electric fields transformed it into slim, parallel capillaries that were strictly perpendicular to the electric field direction. This architectural transformation was accompanied by apoptosis of vascular endothelial cells and a notable reduction in tumour vessel number. Additionally, we found that the anti-angiogenesis and tumour-suppression effects of electric fields synergised with bevacizumab. The anti-angiogenic mechanisms of electric fields include disrupting spindle formation during endothelial cell division and downregulating environmental angiogenesis-related cytokines, such as interleukin-6, CXCL-1, 2, 3, 5 and 8, and matrix metalloproteinases. In summary, our findings demonstrate the potential of alternating electric fields (AEFs) as a therapeutic modality to impede angiogenesis and restrain cancer growth.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.