Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Pulmonary and Critical Care Medicine, Weihai Municipal Hospital, Weihai, China.
Thorac Cancer. 2022 Jan;13(2):257-264. doi: 10.1111/1759-7714.14261. Epub 2021 Dec 2.
This study aimed to evaluate the inhibitory effects and potential mechanisms of icotinib combined with antiangiogenic drugs on lung adenocarcinoma in vivo.
A total of 72 mouse xenograft models established with human lung adenocarcinoma cells (HCC827) were randomly divided into six groups, including control, icotinib (Ic), bevacizumab (Bev), recombinant human endostatin (En), Ic + Bev and Ic + En groups. Mouse weights and tumor volumes were measured regularly. Half of the nude mice in each group were sacrificed after 16 days of drug treatment. The remaining animals were observed for another 16 days without drug supply. Immunohistochemical staining was performed to detect microvessel density in tumor heart, liver, brain specimens from the nude mice and Ki67 expression. Differential expression of vascular endothelial growth factor (VEGFA) in tumor tissue specimens was determined by ELISA and Western blot.
The results showed that the combined drugs inhibited tumor growth more substantially compared with single drugs, without increasing the toxic effects. The antiangiogenesis effect of the combination was better than that of single drug treatment. In addition, both types of targeted drugs and combination medication not only significantly reduced microvessel density in the tumor tissue itself, but also had a certain impact on decreasing microvessel density in the liver. The combination decreased VEGFA and Ki-67 amounts significantly more than icotinib or endostatin as a monotherapy.
Icotinib combined with bevacizumab or rh-endostatin has a stronger inhibitory effect on tumor growth than single-target drug in vivo, with no additional side effects.
本研究旨在评估厄洛替尼联合抗血管生成药物对体内肺腺癌的抑制作用及潜在机制。
将人肺腺癌细胞（HCC827）建立的 72 只小鼠异种移植模型随机分为 6 组，分别为对照组、厄洛替尼（Ic）组、贝伐珠单抗（Bev）组、重组人血管内皮抑制素（En）组、Ic+Bev 组和 Ic+En 组。定期测量小鼠体重和肿瘤体积。每组中的一半裸鼠在药物治疗 16 天后处死。其余动物在没有药物供应的情况下再观察 16 天。免疫组织化学染色检测裸鼠心脏、肝脏、脑组织标本中的微血管密度和 Ki67 表达。酶联免疫吸附试验（ELISA）和 Western blot 检测肿瘤组织标本中血管内皮生长因子（VEGFA）的差异表达。
结果表明，联合用药比单药治疗更能显著抑制肿瘤生长，且不增加毒副作用。联合用药的抗血管生成作用优于单药治疗。此外，两种靶向药物联合用药不仅明显降低了肿瘤组织本身的微血管密度，而且对肝脏的微血管密度也有一定的影响。与单药治疗相比，联合用药显著降低了 VEGFA 和 Ki-67 的含量。
厄洛替尼联合贝伐珠单抗或 rh-endostatin 对体内肿瘤生长的抑制作用强于单靶药物，且无额外的副作用。
