智慧健康2024,Vol.10Issue(5) :167-170.DOI:10.19335/j.cnki.2096-1219.2024.05.042

奥希替尼联合阿帕替尼延缓T790M突变非小细胞肺癌奥希替尼耐药的研究

Osimertinib Combined with Apatinib Delays Osimertinib Resistance in T790M Mutated Non-small Cell Lung Cancer

邓彩旧 樊艳华 罗希 于倩
智慧健康2024,Vol.10Issue(5) :167-170.DOI:10.19335/j.cnki.2096-1219.2024.05.042

奥希替尼联合阿帕替尼延缓T790M突变非小细胞肺癌奥希替尼耐药的研究

Osimertinib Combined with Apatinib Delays Osimertinib Resistance in T790M Mutated Non-small Cell Lung Cancer

邓彩旧 1樊艳华 1罗希 1于倩1
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作者信息

  • 1. 广州市番禺区中心医院,广东 广州 511400
  • 折叠

摘要

目的 分析奥希替尼联合阿帕替尼延缓T790M突变非小细胞肺癌(NSCLC)奥希替尼耐药的临床效果.方法 构建19外显子缺失/T790M突变NSCLC小鼠移植瘤模型,将造模成功的80只小鼠采用随机数字表法分为空白对照组、阿帕替尼单药组、奥希替尼单药组、联合组,每组20只.比较四组小鼠肿瘤生长情况以及EGFR、VEGF/VEGFR等信号传导通路相关蛋白表达情况.结果 给药前,四组肿瘤体积比较差异无统计学意义(P>0.05);给药30d,与给药前相比,阿帕替尼单药组、奥希替尼单药组及联合组肿瘤体积均缩小,同时小于空白对照组,而空白对照组肿瘤体积则增大(P<0.05).与空白对照组相比,阿帕替尼单药组、奥希替尼单药组及联合组Ki-67、EGFR、VEGFR蛋白以及mTOR、AKT、ERK蛋白表达水平均显著下降(P<0.05).结论 奥希替尼联合阿帕替尼可明显抑制T790M突变NSCLC小鼠肿瘤生长,提高奥希替尼治疗敏感性,延缓耐药,其机制可能与抑制EGFR及VEGF/VEGFR信号传导通路有关.

Abstract

Objective To analyze the clinical effect of Osimertinib combined with Apatinib in delaying Osimertinib resistance in T790M mutated non-small cell lung cancer(NSCLC).Methods A 19 exon-deletion/T790M mutated NSCLC mouse transplanted tumor model was established,and 80 mice were divided into blank control group,Apatinib monotherapy group,Osimertinib monotherapy group and combination group by random number table method,with 20 mice in each group.The tumor growth and the expression of EGFR,VEGF/VEGFR and other signal transduction pathways were compared among the four groups.Results Before administration,there was no significant difference in tumor volume among the four groups(P>0.05).After 30 days of administration,compared with before administration,the tumor volume of Apatinib monotherapy group,Osimertinib monotherapy group and combination group decreased,and was smaller than that of blank control group,while the tumor volume of blank control group increased,P<0.05.Compared with the blank control group,the expression levels of Ki-67,EGFR,VEGFR and mTOR,AKT and ERK proteins in Apatinib monotherapy group,Osimertinib monotherapy group and combination group were significantly decreased.P<0.05.Conclusion Osimertinib combined with Apatinib can significantly inhibit the tumor growth of T790M mutant NSCLC mice,improve the treatment sensitivity of Osimertinib,and delay drug resistance.The mechanism may be related to the inhibition of EGFR and VEGF/VEGFR signaling pathways.

关键词

非小细胞肺癌/T790M突变/奥希替尼/阿帕替尼/耐药

Key words

Non-small cell lung cancer/T790M mutation/Osimertinib/Apatinib/Resistant

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基金项目

番禺区科技计划医疗卫生项目(2020)(2020-Z04-030)

出版年

2024
智慧健康

智慧健康

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