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Erlotinib Activates Different Cell Death Pathways in EGFR-mutant Lung Cancer Cells Grown in 3D Versus 2D Culture Systems.
Lee, Hyun-Kyung; Noh, Min Hye; Hong, Seung-Woo; Kim, Seung-Mi; Kim, Sung Hyun; Kim, Yeong Seok; Broaddus, V Courtney; Hur, Dae Young.
Afiliación
  • Lee HK; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea.
  • Noh MH; Department of Anatomy and Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea.
  • Hong SW; Department of Anatomy and Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea.
  • Kim SM; Department of Anatomy and Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea.
  • Kim SH; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea.
  • Kim YS; Department of Anatomy and Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea.
  • Broaddus VC; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, U.S.A.
  • Hur DY; Department of Anatomy and Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea; dyhur@inje.ac.kr Courtney.Broaddus@ucsf.edu.
Anticancer Res ; 41(3): 1261-1269, 2021 Mar.
Article en En | MEDLINE | ID: mdl-33788717
BACKGROUND/AIM: Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation have been shown to have a good response to erlotinib, a receptor tyrosine kinase inhibitor of EGFR. In this study, we found that the cell death pathways activated by erlotinib in 2D and 3D culture systems are different. MATERIALS AND METHODS: The cell death pathways induced by erlotinib were evaluated by flow cytometry and immunoblotting in both 2D and 3D culture systems of EGFR mutant lung cancer cells. RESULTS: Treatment with erlotinib induced caspase 8 activation and up-regulation of TNF-related apoptosis-inducing ligand (TRAIL) expression only in 3D cultures. Knockdown of TRAIL attenuated both erlotinib-induced activation of caspase-8 and apoptosis in 3D cultures. Erlotinib also increased LC3, an autophagy marker, expression and c-Jun N terminal kinase (JNK) activation. Both 3-MA as an autophagy inhibitor and SP600125 as a JNK inhibitor, significantly inhibited erlotinib-induced cell death. CONCLUSION: Erlotinib induces apoptotic cell death in 3D cultures through an autophagy-TRAIL-JNK pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Cultivo de Célula / Clorhidrato de Erlotinib / Neoplasias Pulmonares / Mutación Límite: Humans Idioma: En Revista: Anticancer Res Año: 2021 Tipo del documento: Article Pais de publicación: Grecia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Cultivo de Célula / Clorhidrato de Erlotinib / Neoplasias Pulmonares / Mutación Límite: Humans Idioma: En Revista: Anticancer Res Año: 2021 Tipo del documento: Article Pais de publicación: Grecia