Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer.
Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer.
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Re-188 增强贝伐珠单抗对非小细胞肺癌的抑制作用
DOI：
10.3390/molecules21101308
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发表时间：
2016-09-30
期刊：
影响因子：
--
通讯作者：
Cheng D
中科院分区：
文献类型：
--
作者：
Xiao J;Xu X;Li X;Li Y;Liu G;Tan H;Shen H;Shi H;Cheng D
实体瘤的生长、浸润和转移等恶性行为主要是由肿瘤新生血管滋养的。因此，抗血管生成治疗是控制肿瘤进展的关键。贝伐单抗，一种人源化抗血管内皮生长因子（VEGF）抗体，加上化疗或生物治疗可以延长癌症患者的生存期，但治疗相关的死亡率是一个问题。为了提高对非小细胞肺癌（NSCLC）的抑制效果并减少副作用，我们使用贝伐单抗直接标记的β放射性核素Re-188在人A549肿瘤模型中进行放射免疫治疗。细胞毒性试验数据显示，在不同浓度的188 ReO 4 −或188 Re-贝伐珠单抗作用4和24 h后，细胞活力出现时间和放射性剂量依赖性降低。此外，细胞凋亡测定证实，与对照组和其他治疗组相比，188 Re-贝伐珠单抗组的细胞凋亡更大。在体内，与其他组相比，188 Re-贝伐单抗（11.1 MBq/小鼠）组的肿瘤体积没有减少，但生长延迟。因此，188 Re-贝伐珠单抗增强了贝伐珠单抗的治疗效果，提示了NSCLC治疗的潜在治疗策略。
The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4− or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.
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