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  • ISSN 1674-8301
  • CN 32-1810/R
Volume 39 Issue 1
Jan.  2025
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Liting Lv, Xin Hua, Jiaxin Liu, Sutong Zhan, Qianqian Zhang, Xiao Liang, Jian Feng, Yong Song. Anlotinib reverses osimertinib resistance via inhibiting epithelial-to-mesenchymal transition and angiogenesis in non-small cell lung cancer[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240045
Citation: Liting Lv, Xin Hua, Jiaxin Liu, Sutong Zhan, Qianqian Zhang, Xiao Liang, Jian Feng, Yong Song. Anlotinib reverses osimertinib resistance via inhibiting epithelial-to-mesenchymal transition and angiogenesis in non-small cell lung cancer[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240045
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Anlotinib reverses osimertinib resistance via inhibiting epithelial-to-mesenchymal transition and angiogenesis in non-small cell lung cancer

  • 1.

    Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, China

  • 2.

    Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China

  • 3.

    Southeast University Medical College, Nanjing, Jiangsu, 210003, China

  • 4.

    Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China

  • 5.

    Department of Respiratory and Critical Care Medicine, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China

  • 6.

    Department of Oncology, Affiliated Jiangyin Hospital of Nantong University, Jiangyin, Jiangsu 214400, China

  • 7.

    Department of Pulmonary and Critical Care Medicine, Nantong Key Laboratory of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China

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  • Corresponding author:

    Jian Feng, Department of Pulmonary and Critical Care Medicine, Nantong Key Laboratory of Respiratory Medicine, Affiliated Hospital of Nantong University, Xisi Road #20, Nantong, Jiangsu 226001, China. E-mail: jfeng68@126.com

    Yong Song, Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Nanjing Medical University, Zhongshan Road #305, Nanjing, Jiangsu 210002, China. E-mail: yong.song@nju.edu.cn

  • ρThe authors contributed equally to this work.

  • Received Date: February 20, 2024
  • Revised Date: September 03, 2024
  • Accepted Date: September 09, 2024
    Graphical Abstract
    • Abstract

  • In the present, we aimed to investigate the effect of anlotinib on the potential reversal of osimertinib resistance by inhibiting the formation of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In a clinical case, anlotinib reversed osimertinib resistance in Non-small cell lung cancer (NSCLC). We performed an immunohistochemical experiment on tumor tissues from three non-small cell lung cancer patients exhibiting osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A (VEGFA) before and after 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 the expression in tissues of patients before taking osimertinib. Subsequently, we established osimertinib-resistant cell lines and found that the osimertinib-resistant cells acquired the EMT features. Then, 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 micro-vessels were analyzed in the combination group in vitro. Finally, we explored the reversal of osimertinib resistance in combination with anlotinib in vivo with 20 nude mice. The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of resistant cells, which also inhibited tumor growth, exerted anti-tumor activity, and ultimately reversed osimertinib resistance in mice. The co-administration of osimertinib and anlotinib demonstrated their synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients, ultimately reversing osimertinib resistance.

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  • The authors would like to thank all the reviewers who participated in the review and MJEditor (www.mjeditor.com) for their linguistic assistance during the preparation of this manuscript.

    This work was supported by the National Natural Science Foundation of China (Nos. 82172728 and 82370096).

    CLC number: R734.2, Document code: A

    The authors reported no conflict of interests.

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