[表皮生长因子受体酪氨酸激酶抑制剂对表皮生长因子受体突变型肺癌淋巴管生成的影响]

[Effect of EGFR-TKI on lymphangiogenesis of lung cancer with EGFR mutation].

作者信息

Cai Minghui, Yang Xinying, Jiang Baohong, Teng Fukang, Pan Yan, Mao Feng, Shen-Tu Yang

机构信息

Department of Thoracic Cancer, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai Lung Tumor Clinical Medical Center, Shanghai 200030, China.

Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai 201203, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2014 Dec;17(12):834-8. doi: 10.3779/j.issn.1009-3419.2014.12.02.

DOI:10.3779/j.issn.1009-3419.2014.12.02

PMID:25539607

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6000415/

Abstract

BACKGROUND AND OBJECTIVE

This study aims to explore the effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) on the lymphangiogenesis of lung cancer with EGFR mutation, as well as to determine the function of EGFR targeted therapy in relation to the inhibition of lymphangiogenesis during lung cancer treatment.

METHODS

The EGFR double mutant lung cancer cell line NCI-H1975 is used to construct lung cancer xenograft models. The models are divided into two groups: the solvent control group and the EGFR-TKI treatment group. Each group includes five mice. The inhibitory effect of EGFR-TKI on the growth of transplanted tumors was observed. Immunohistochemical method and lymphatic endothelium specific antibody D2-40 were used in the experiment to observe the influence of EGFR-TKI on lymphangiogenesis in lung cancer.

RESULTS

The weight and relative volume of tumors in the EGFR-TKI treated group were less than those in the solvent control group. The average lymphatic vessel density of EGFR-TKI-treated mice was 6.44 per case. This value was 10.70 per case in the solvent control group. Lower density of lymphangiogenesis was found in the EGFR-TKI treated group (P=0.023). The area and longest diameter of neonatal lymphatic vessel of the EGFR-TKI treated group were less than those of the solvent control group. Moreover, EGFR-TKI exhibited no significant effect on the invasion of tumor cells into the lymphatic vessel (P=0.519).

CONCLUSIONS

EGFR-TKI can inhibit lymphangiogenesis in EGFR mutant lung cancer while suppressing vessel diameter and expansion area.

摘要

背景与目的

本研究旨在探讨表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）对表皮生长因子受体（EGFR）突变型肺癌淋巴管生成的影响，并确定EGFR靶向治疗在肺癌治疗过程中对抑制淋巴管生成的作用。

方法

采用EGFR双突变肺癌细胞系NCI-H1975构建肺癌异种移植模型。将模型分为两组：溶剂对照组和EGFR-TKI治疗组。每组包括5只小鼠。观察EGFR-TKI对移植瘤生长的抑制作用。实验采用免疫组织化学方法和淋巴管内皮特异性抗体D2-40，观察EGFR-TKI对肺癌淋巴管生成的影响。

结果

EGFR-TKI治疗组肿瘤重量和相对体积均小于溶剂对照组。EGFR-TKI治疗组小鼠平均淋巴管密度为每例6.44条。溶剂对照组该值为每例10.70条。EGFR-TKI治疗组淋巴管生成密度较低（P=0.023）。EGFR-TKI治疗组新生淋巴管面积和最长径均小于溶剂对照组。此外，EGFR-TKI对肿瘤细胞侵入淋巴管无显著影响（P=0.519）。