Effects of quercetin combined with anticancer drugs on metastasis-associated factors of gastric cancer cells: in vitro and in vivo studies
Journal
Journal of Nutritional Biochemistry
Journal Volume
51
Pages
105-113
Date Issued
2018
Author(s)
Abstract
Chemotherapy is essential to most patients with gastric cancer and the anticancer drug, irinotecan (CPT-11), and its metabolite, SN-38, an inhibitor of DNA topoisomerase I, are first-line chemotherapies for gastric cancer. Quercetin, a flavonoid that is widely found in various vegetables and fruits, has the ability to potentiate the efficacy of anticancer drugs. The purpose of this study was to investigate the therapeutic effect of quercetin combined with irinotecan/SN-38 in the AGS human gastric cancer cell line in vitro and in vivo. The in vitro study evaluated the efficacy of high-dose SN-38 and quercetin combined with low-dose SN-38 on cell viability, apoptosis, and β-catenin expression. Results showed that cell viability and the percentage of apoptosis in combined treatments with quercetin and SN-38 were comparable to treatment with high-dose SN-38 alone. AGS cells treated with a high dose of SN-38 exhibited up-regulation of β-catenin protein expression, whereas quercetin-treated cells (either quercetin alone or combined with low-dose SN-38) exhibited lower protein levels of β-catenin. In the AGS xenograft mouse model, gene expression of cyclooxygenase-2 and epithelial-mesenchymal transition-related markers, such as Twist1 and ITGβ6, were lower in combined treatments with quercetin and low-dose irinotecan than high-dose irinotecan alone. Furthermore, the concentration of angiogenesis-associated factors (vascular endothelial growth factor (VEGF)-A and VEGF-receptor 2) and percentage of Tie2-expressing monocytes was significantly down-regulated in combined treatments with quercetin and irinotecan. These results suggest that quercetin may enhance the efficacy of irinotecan/SN-38 in the human AGS cell line. ? 2017 Elsevier Inc.
Subjects
Angiogenesis; Gastric cancer; Irinotecan/SN-38; Metastasis; Quercetin
SDGs
Other Subjects
angiopoietin receptor; beta catenin; cyclooxygenase 2; firtecan; irinotecan; quercetin; transcription factor Slug; transcription factor Snail; Twist related protein 1; uvomorulin; vasculotropin A; vasculotropin receptor 2; antineoplastic agent; camptothecin; DNA topoisomerase inhibitor; irinotecan; quercetin; tumor protein; AGS cell line; animal experiment; animal model; apoptosis; Article; cancer combination chemotherapy; cell survival; cell viability; controlled study; down regulation; drug efficacy; drug megadose; epithelial mesenchymal transition; extracellular matrix; female; gene expression; human; human cell; in vitro study; in vivo study; low drug dose; metastasis; monocyte; mouse; nonhuman; protein expression; stomach cancer; therapy effect; tumor growth; tumor volume; tumor xenograft; upregulation; adenocarcinoma; analogs and derivatives; animal; comparative study; drug effect; drug screening; gene expression regulation; genetics; germfree animal; intraperitoneal drug administration; metabolism; nude mouse; pathology; randomization; secondary; stomach tumor; tumor cell line; Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Camptothecin; Cell Line, Tumor; Cell Survival; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Humans; Injections, Intraperitoneal; Mice, Nude; Neoplasm Proteins; Quercetin; Random Allocation; Specific Pathogen-Free Organisms; Stomach Neoplasms; Topoisomerase I Inhibitors; Tumor Burden; Xenograft Model Antitumor Assays
Publisher
Elsevier Inc.
Type
journal article