重组人血管内皮抑素增强EGFR-TKIs对肺癌的抗瘤作用

doi:10.6040/j.issn.1671-7554.0.2018.535

摘要/Abstract

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。

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

Abstract: 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 L858R and T790M)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= 山东大学学报 (医学版)56卷9期 -石树远,等.重组人血管内皮抑素增强EGFR-TKIs对肺癌的抗瘤作用 \=-0.112), and erlotinib could inhibit the tumor cell growth (P=0.018). Meanwhile, 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 T790M-related drug resistance. Endostar combined with erlotinib has a promising application prospect for patients with EGFR-TKIs resistance.

Key words: Recombinant human vascular endostatin, Epidermal growth factor receptor tyrosine kinase inhibitor, Resistant

中图分类号:

R734.2

石树远,关志宇,孙大强. 重组人血管内皮抑素增强EGFR-TKIs对肺癌的抗瘤作用[J]. 山东大学学报 (医学版), 2018, 56(9): 6-10.

SHI Shuyuan, GUAN Zhiyu, SUN Daqiang. Recombinant human vascular endostatin enhances antitumour activity of EGFR-TKIs for lung cancer[J]. Journal of Shandong University (Health Sciences), 2018, 56(9): 6-10.

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