Anlotinib reverses osimertinib resistance by inhibiting epithelial-to-mesenchymal transition and angiogenesis in non-small cell lung cancer
Liting Lyu1
Xin Hua2
Jiaxin Liu3
Sutong Zhan4
Qianqian Zhang5
Xiao Liang6
Jian Feng7
Yong Song5
1.Department of Respiratory and Critical Care Medicine,Affiliated Jinling Hospital,Nanjing Medical University,Nanjing,Jiangsu 210002,China;Department of Oncology,Affiliated Hospital of Nantong University,Nantong,Jiangsu 226001,China2.Southeast University Medical College,Nanjing,Jiangsu 210003,China3.Department of Respiratory and Critical Care Medicine,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210008,China4.Department of Respiratory and Critical Care Medicine,Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210002,China5.Department of Respiratory and Critical Care Medicine,Affiliated Jinling Hospital,Nanjing Medical University,Nanjing,Jiangsu 210002,China6.Department of Oncology,Affiliated Jiangyin Hospital of Nantong University,Jiangyin,Jiangsu 214400,China7.Department of Pulmonary and Critical Care Medicine,Nantong Key Laboratory of Respiratory Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu 226001,China
摘要：In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.
机标关键词：osimertinibcancercellangiogenesisanlotinibepithelialinhibitinglung
分类号：R734.2(呼吸系肿瘤)
论文发表日期：2025-09-30
在线出版日期：2025-12-01（本平台首次上网日期，不代表文献的发表时间）
页数：15( 452-466 )
英文信息