2. Academic Validation
  3. Inhibition of CDCP1 by 8-isopentenylnaringenin synergizes with EGFR inhibitors in lung cancer treatment

Inhibition of CDCP1 by 8-isopentenylnaringenin synergizes with EGFR inhibitors in lung cancer treatment

  • Mol Oncol. 2023 Apr 4. doi: 10.1002/1878-0261.13429.
Sze-Ching Wong # 1 2 3,  Chun-Chieh Yeh # 4 5,  Xun-Yu Zhang 1,  Chih-Ying Hsieh 1,  Chia-Chien Lo 6,  Ting-Ting Kuo 2 3,  Ching-Chan Lin 7,  Chih-Hua Chao 8 9,  Jing-Pei Liu 1,  Ling-Chu Chang 6,  Lu-Hai Wang 2 3 10,  Yuh-Pyng Sher 1 2 3 6
Affiliations

Affiliations

  • 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404333, Taiwan.
  • 2 Chinese Medicine Research Center, China Medical University, Taichung, 404333, Taiwan.
  • 3 Research Center for Chinese Herbal Medicine, China Medical University, Taichung, 404333, Taiwan.
  • 4 Department of Medicine, School of Medicine, China Medical University, Taichung, 404333, Taiwan.
  • 5 Department of Surgery, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan.
  • 6 Center for Molecular Medicine, China Medical University Hospital, Taichung, 404327, Taiwan.
  • 7 Division of Hematology and Oncology, China Medical University Hospital, Taichung, 404332, Taiwan.
  • 8 School of Pharmacy, China Medical University, Taichung, 406040, Taiwan.
  • 9 Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, 404332, Taiwan.
  • 10 Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
  • # Contributed equally.
PMID: 37013960 DOI: 10.1002/1878-0261.13429
Abstract

CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance by regulating EGFR signaling pathways and is a potential target in lung Cancer treatment. This study aims to identify a CDCP1 reducer that synergistically improves TKI treatment. Utilizing a high-throughput drug screening system, a phytoestrogen 8-isopentenylnaringenin (8PN) was identified. Upon 8PN treatment, CDCP1 protein levels and malignant features were reduced. 8PN exposure caused the accumulation of lung Cancer cells in G0/G1 phase and increased the proportion of senescent cells. In EGFR TKI-resistant lung Cancer cells, the combination of 8PN and TKI synergistically reduced cell malignance, inhibited downstream EGFR pathway signaling and exerted additive effects on cell death. Moreover, combination therapy effectively reduced tumor growth and enhanced tumor necrosis in tumor xenograft mice models. Mechanistically, 8PN increased interleukin (IL)6 and IL8 expression, induced neutrophil infiltration, and enhanced neutrophil-mediated cytotoxicity to attenuate lung Cancer cell growth. In conclusion, 8PN enhances the anti-cancer efficacy of EGFR TKI on lung Cancer, and triggers neutrophil-dependent necrosis, highlighting the potential to overcome TKI resistance in lung Cancer patients who have EGFR mutation.

Keywords

8-isopentenylnaringenin; EGFR TKI acquired resistance; lung adenocarcinoma; necrosis; synergistic effects.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15772
    99.96%, EGFR 抑制剂
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