长春瑞滨联合西妥昔单抗在体内外的抗血管生成作用

[Anti-angiogenic effect of vinorelbine in combination with cetuximab in vitro and in vivo].

作者信息

Qian Xiao-ping, Liu Bao-rui, Wan Li, Hu Jing, Zhu Li-jing, Yu Li-xia

机构信息

Cancer Center of Nanjing University Medical School Affiliated Drum Tower Hospital, Oncology Institutes of Nanjing University, Jiangsu Province Key Laboratory of Molecular Medical Technology, Nanjing 210008, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2010 Apr;32(4):253-7.

PMID:20510073

Abstract

OBJECTIVE

This experiment aims to study the anti-angiogenic ability of vinorelbine combined with cetuximab in vitro and in vivo.

METHODS

Human lung adenocarcinoma A549 cells were used as control group. Proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by MTT assay. Furthermore, we used Transwell chambers, capillary tube formation and flow cytometry to observe the effects of vinorelbine combined with cetuximab on HUVEC migration, tube formation and cell apoptosis, respectively. In addition, the anti-angiogenic ability of the drugs was checked using chicken chorioallantoic membrane (CAM) model.

RESULTS

The inhibitory rate of HUVEC growth was 25.8%, 39.2%, 54.0% for vinorelbine at the concentration of 0.1 ng/ml, 0.4 ng/ml, and 0.8 ng/ml, respectively; that of 0.25 microg/ml cetuximab was 19.7%, and that of 0.1 ng/ml vinorelbine + 0.25 microg/ml cetuximab, 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab and 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 29.5%, 46.4%, 64.6%, respectively. The inhibitory rates of the drugs at the above mentioned combinations of migration and tube formation of HUVEC were 51.9%, 68.2%, 95.0%, respectively. The inhibitory rate of 0.1 ng/ml + 0.25 microg/ml cetuximab and 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab on tube formation of HUVEC was 38.8% and 57.7%, respectively, showing a sub-additive effect, and that of combination of 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 78.9%, showing a synergistic effect. In addition, the apoptotic rate of HUVEC induced by 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 59.9%, showing a synergistic effect. The in vivo experiment also showed that the combination of the two drugs had a synergistic anti-angiogenic effect.

CONCLUSION

Both low dose vinorelbine and cetuximab have an anti-angiogenic effect in vitro and in vivo, and the combination of the two drugs has sub-additive or synergistic inhibitory effect on angiogenesis.

摘要

目的

本实验旨在研究长春瑞滨联合西妥昔单抗在体外和体内的抗血管生成能力。

方法

以人肺腺癌A549细胞作为对照组。采用MTT法评估人脐静脉内皮细胞（HUVEC）的增殖情况。此外，我们分别使用Transwell小室、毛细血管管腔形成实验和流式细胞术观察长春瑞滨联合西妥昔单抗对HUVEC迁移、管腔形成及细胞凋亡的影响。另外，使用鸡胚绒毛尿囊膜（CAM）模型检测药物的抗血管生成能力。

结果

长春瑞滨浓度为0.1 ng/ml、0.4 ng/ml和0.8 ng/ml时，对HUVEC生长的抑制率分别为25.8%、39.2%、54.0%；0.25 μg/ml西妥昔单抗的抑制率为19.7%；0.1 ng/ml长春瑞滨 + 0.25 μg/ml西妥昔单抗、0.4 ng/ml长春瑞滨 + 0.25 μg/ml西妥昔单抗和0.8 ng/ml长春瑞滨 + 0.25 μg/ml西妥昔单抗的抑制率分别为29.5%、46.4%、64.6%。上述药物组合对HUVEC迁移和管腔形成的抑制率分别为51.9%、68.2%、95.0%。0.1 ng/ml + 0.25 μg/ml西妥昔单抗和0.4 ng/ml长春瑞滨 + 0.25 μg/ml西妥昔单抗对HUVEC管腔形成的抑制率分别为38.8%和57.7%，呈亚相加效应；0.8 ng/ml长春瑞滨 + 0.25 μg/ml西妥昔单抗的抑制率为78.9%，呈协同效应。此外，0.8 ng/ml长春瑞滨 + 0.25 μg/ml西妥昔单抗诱导HUVEC的凋亡率为59.9%，呈协同效应。体内实验也表明两种药物联合具有协同抗血管生成作用。