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Inhibitor of ghrelin receptor reverses gefitinib resistance in lung cancer

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Abstract

Gefitinib is the first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), which is used in the treatment of NCSLC patients through interrupting EGFR signaling pathway. Although gefitinib prolongs patients’ progression-free survival (PFS), acquired resistance occurs in advanced NSCLC patients. In this study, we mainly investigated the effects of antagonist for ghrelin-R (d-lys-3-GHRP-6) on conquering acquired gefitinib resistance in human lung cancer cells. We found that GHSR was overexpressed in our established HCC827/GR cells compared with parental cells, accompanied with increase of p-AKT and p-ERK1/2. Treatment of d-lys-3-GHRP-6 significantly decreased p-AKT and p-ERK1/2 expression in HCC827/GR cells. H1650 cells and HCC827/GR cells were treated with control, gefitinib, d-lys-3-GHRP-6 and d-lys-3-GHRP-6 + gefitinib, respectively. In H1650 and HCC827/GR cells, combination of d-lys-3-GHRP-6 and gefitinib significantly inhibited cell proliferation and Bcl2 protein level, induced the cell apoptosis and cleaved-caspase3 protein level compared with control group, while there was no significant difference between control and gefitinib group.

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Author notes

  1. Xiaoyou Li and Xia Zhao contributed equally to the present study.

Authors and Affiliations

  1. Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210000, China

    Xiaoyou Li, Chenchen Li, Siwen Liu, Fei Yan, Yue Teng & Jifeng Feng

  2. Department of Oncology, First People’s Hospital, Yancheng, Fourth Affiliated Hospital, Nantong University, Yancheng, 224001, China

    Xia Zhao

  3. State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, No. 101 Longmian Road, Nanjing, 210000, China

    Dengshun Miao

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  1. Xiaoyou Li
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  2. Xia Zhao
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  3. Chenchen Li
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  4. Siwen Liu
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  5. Fei Yan
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Correspondence to Jifeng Feng or Dengshun Miao.

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Li, X., Zhao, X., Li, C. et al. Inhibitor of ghrelin receptor reverses gefitinib resistance in lung cancer. Human Cell 32, 360–366 (2019). https://doi.org/10.1007/s13577-019-00245-5

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  • DOI: https://doi.org/10.1007/s13577-019-00245-5

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