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Intrapulmonary inoculation of multicellular spheroids to construct an orthotopic lung cancer xenograft model that mimics four clinical stages of non-small cell lung cancer.

Authors
  • Huang, Yingbo1
  • Lu, Yifan2
  • Vadlamudi, Mallika3
  • Zhao, Shen4
  • Felmlee, Melanie5
  • Rahimian, Roshanak6
  • Guo, Xin7
  • 1 Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: [email protected]
  • 2 Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: [email protected]
  • 3 Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: [email protected]
  • 4 Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: [email protected]
  • 5 Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: [email protected]
  • 6 Department of Physiology and Pharmacology, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: [email protected]
  • 7 Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: [email protected]
Type
Published Article
Journal
Journal of pharmacological and toxicological methods
Publication Date
Jan 01, 2020
Volume
104
Pages
106885–106885
Identifiers
DOI: 10.1016/j.vascn.2020.106885
PMID: 32531198
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Lung cancer leads in mortality among all types of cancer in US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Mice models of lung cancer based on subcutaneous or orthotopic inoculation of cancer cell suspension do not adequately mimic the progression of lung cancer in clinic. A549-iRFP cells (human NSCLC adenocarcinoma) were cultured to form multicellular spheroids (MCS), which were then inoculated intrapulmonarily into male athymic nude mice. The xenograft cancer development was monitored by in vivo fluorescent imaging and validated by open-chest anatomy, ex vivo fluorescent imaging, and histological studies. The newly developed orthotopic xenograft model of lung cancer simulated all four clinical stages of NSCLC progression over one month: Stage 1) localized tumor at the inoculation site, Stage 2) multiple tumor nodules or larger tumor nodule on the same side of the lung, Stage 3) cancer growth on heart surface, and Stage 4) metastatic cancer on both sides of the lung. The model yielded high rates of postoperative survival (100%) and parenchymal tumor establishment (88.9%). The roughness of the inoculated MCS associated negatively with the time needed to develop metastatic cancer (p = .0299). This new orthotopic xenograft model of NSCLC would facilitate the development of medications to treat lung cancer. Copyright © 2020. Published by Elsevier Inc.

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