EGFR-TKI对肺癌新生淋巴管的影响及其意义

Effect of EGFR-TKI on Lymphangiogenesis of Lung Cancer with EGFR Mutation

背景与目的探索表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)对EGFR突变肺癌新生淋巴管的影响,探讨靶点治疗对新生淋巴管的抑制作用及其在肺癌治疗中所发挥的作用。方法采用EGFR双位点突变的NCI-H1975肺癌细胞株构建小鼠移植瘤模型。设立溶剂对照组和EGFR-TKI给药组,每组5只小鼠,观察EGFR-TKI对小鼠移植瘤的生长抑制作用;运用淋巴管内皮特异性抗体D2-40,采用免疫组织化学的方法,观察新生淋巴管的密度、面积、最大径,探讨EGFR-TKI对于肺癌组织淋巴管新生的影响。结果 EGFR-TKI给药组小鼠肿瘤重量、肿瘤相对体积小于溶剂对照组。EGFR-TKI给药组小鼠平均新生淋巴管密度为6.44个/例,溶剂对照组小鼠平均新生淋巴管密度为10.70个/例,EGFR-TKI给药组小鼠平均新生淋巴管密度较低(P=0.023)。EGFR-TKI给药组小鼠新生淋巴管面积、最长径小于溶剂对照组。而EGFR-TKI对新生淋巴管的肿瘤细胞侵犯没有明显影响(P=0.519)。结论 EGFR-TKI可以抑制EGFR突变肺癌组织淋巴管的新生,抑制新生淋巴管管径及面积的扩大。

Background and objective hTis study aims to explore the effect of epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKIs） on the lymphangiogenesis of lung cancer withEGFR mutation, as well as to determine the function of EGFR targeted therapy in relation to the inhibition of lymphangiogenesis during lung cancer treatment.Methods hTeEGFR double mutant lung cancer cell line NCI-H1975 is used to construct lung cancer xenogratf models. hTe models are divided into two groups：the solvent control group and the EGFR-TKI treatment group. Each group includes ifve mice. hTe inhibitory effect of EGFR-TKI on the growth of transplanted tumors was observed. Immunohistochemical method and lymphatic endothelium speciifc antibody D2-40 were used in the experiment to observe the inlfuence of EGFR-TKI on lymphangiogenesis in lung cancer.Results hTe weight and relative volume of tumors in the EGFR-TKI treated group were less than those in the solvent control group. hTe average lymphatic ves-sel density of EGFR-TKI-treated mice was 6.44 per case. hTis 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）. hTe 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 signiifcant effect on the invasion of tumor cells into the lymphatic vessel （P=0.519）.Conclusion EGFR-TKI can inhibit lymphangiogenesis inEGFR mutant lung cancer while suppressing vessel diameter and expansion area.