重组人血管内皮抑素增强EGFR-TKIs对肺癌的抗瘤作用  

Recombinant human vascular endostatin enhances antitumour activity of EGFR-TKIs for lung cancer

作　　者：石树远 关志宇[1] 孙大强[2] SHI Shuyuan;GUAN Zhiyu;SUN Daqiang(Department of Thoracic Surgery,The Second Hospital of Tianjin Medical University,Tianjin 300211,China;Department of Thoracic Surgery,Tianjin Chest Hospital,Tianjin 300051,China)

机构地区：[1]天津医科大学第二医院胸外科,天津300211 [2]天津市胸科医院,天津300051

出　　处：《山东大学学报（医学版）》2018年第9期6-10,共5页Journal of Shandong University:Health Sciences

基　　金：天津市卫生局科技基金(2013KZ109)

摘　　要：目的研究重组人血管内皮抑素(恩度)联合表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)厄洛替尼对EGFR-TKIs耐药细胞系H1975(携带L858R和T790M)在体外及裸鼠移植瘤的抑制作用。方法对H1975细胞株进行细胞活性测定,确定厄洛替尼单药、恩度单药及厄洛替尼+恩度各组的吸光度值。建立H1975肺癌细胞系裸鼠移植瘤模型,将裸鼠随机分为4组(对照组、厄洛替尼组、恩度组及联合用药组),每组6只。从给药开始每3天测1次肿瘤直径,2周后处死所有实验鼠,取出肿瘤,测量、拍照。结果体外细胞实验中,厄洛替尼单药对H1975细胞增殖抑制作用差异有统计学意义(P=0.043),恩度单药对H1975细胞增殖的抑制作用差异无统计学意义(P=0.261),厄洛替尼+恩度的效应与单用厄洛替尼重合。体内动物实验中,恩度组不能抑制肿瘤细胞生长(P=0.112),厄洛替尼组可抑制肿瘤细胞生长(P=0.018),而联合用药组两药有协同作用(P=0.048)。组间两两比较结果显示,联合用药与对照组和厄洛替尼组之间差异有统计学意义(P=0.046,P=0.023)。结论恩度联合厄洛替尼可增强厄洛替尼的抗肿瘤作用,逆转T790M相关耐药;恩度联合厄洛替尼针对EGFR-TKIs耐药患者应用前景广阔。Objective To study the inhibitory effect of recombinant human vascular endostatin（ endostar） combined with epidermal growth factor receptor tyrosine kinase inhibitor（ EGFR-TKI）,erlotinib,on the resistant cell lines of EGFR-TKIs H1975（ with L858 R and T790 M） in vitro and in vivo. Methods The cell activity of H1975 cell line was detected,and the absorbance values of erlotinib,endostar and erlotinib ＋ endostar were determined. The xenograft tumor model of H1975 lung cancer cell line was established,and the nude mice were randomly divided into 4 groups（control group,erlotinib group,endostar group and combined medication group）,6 in each group. The tumor diameter was measured once every 3 days since the administration of the drug,and all the experimental mice were executed 2 weeks later. The tumors were taken out,measured and photographed. Results Cell experiments in vitro showed that,erlotinib had a statistically significant inhibitory effect on H1975 cell proliferation（ P = 0. 043）,while endostar had no statistically significant inhibitory effect on H1975 cell proliferation（ P = 0. 261）. The effect of erlotinib ＋ endostar coincided with erlotinib. The animal experiments in vivo showed that,endostar could not inhibit the tumor cell growth（ P= 0. 112）,and erlotinib could inhibit the tumor cell growth（ P = 0. 018）. M eanwhile,the two drugs exhibited a synergistic effect（ P = 0. 048）. Further pairwise comparison showed statistically significant differences between the combined medication group and control group/erlotinib group（ P = 0. 046,P = 0. 023）. Conclusion Endostar combined with erlotinib can enhance antitumour activity of erlotinib for lung cancer and reverse the T790 M-related drug resistance. Endostar combined with erlotinib has a promising application prospect for patients with EGFR-TKIs resistance.

关 键 词：重组人血管内皮抑素 表皮生长因子受体酪氨酸激酶抑制剂 耐药 

分 类 号：R734.2[医药卫生—肿瘤]