Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI
Journal
PLoS ONE
Journal Volume
12
Journal Issue
11
Pages
e0187824
Date Issued
2017
Author(s)
Abstract
This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (Ktrans, kep, and iAUC90) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size. Ktrans and iAUC90 significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas kep decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC90 between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle. ? 2017 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
bevacizumab; epidermal growth factor receptor; erlotinib; gefitinib; angiogenesis inhibitor; antineoplastic agent; bevacizumab; contrast medium; EGFR protein, human; epidermal growth factor receptor; erlotinib; protein kinase inhibitor; adenocarcinoma; animal experiment; animal model; animal tissue; apoptosis; apparent diffusion coefficient; area under the curve; Article; cancer chemotherapy; cancer inhibition; capillary density; controlled study; diffusion weighted imaging; disease association; drug response; dynamic contrast-enhanced magnetic resonance imaging; HCC827 cell line; in vivo study; lung cancer; lung perfusion; mouse; mouse model; multiple cycle treatment; nonhuman; potassium transport; tumor growth; tumor necrosis; tumor volume; animal; cell proliferation; cell survival; diagnostic imaging; drug effects; drug resistance; drug screening; gene deletion; genetics; human; lung tumor; molecularly targeted therapy; nuclear magnetic resonance imaging; pathology; procedures; treatment outcome; tumor cell line; Angiogenesis Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cell Line, Tumor; Cell Proliferation; Cell Survival; Contrast Media; Drug Resistance, Neoplasm; Erlotinib Hydrochloride; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Mice; Molecular Targeted Therapy; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor; Sequence Deletion; Treatment Outcome; Tumor Burden; Xenograft Model Antitumor Assays
Publisher
Public Library of Science
Type
journal article