TY - JOUR
T1 - Effects of quercetin combined with anticancer drugs on metastasis-associated factors of gastric cancer cells
T2 - in vitro and in vivo studies
AU - Lei, Cing Syuan
AU - Hou, Yu Chen
AU - Pai, Man Hui
AU - Lin, Ming Tsan
AU - Yeh, Sung Ling
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Gastric cancer
KW - Irinotecan/SN-38
KW - Metastasis
KW - Quercetin
KW - Tumor Burden/drug effects
KW - Topoisomerase I Inhibitors/administration & dosage
KW - Humans
KW - Antineoplastic Agents, Phytogenic/administration & dosage
KW - Cell Survival/drug effects
KW - Camptothecin/administration & dosage
KW - Stomach Neoplasms/drug therapy
KW - Neoplasm Proteins/genetics
KW - Epithelial-Mesenchymal Transition/drug effects
KW - Female
KW - Adenocarcinoma/drug therapy
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Specific Pathogen-Free Organisms
KW - Apoptosis/drug effects
KW - Injections, Intraperitoneal
KW - Gene Expression Regulation, Neoplastic/drug effects
KW - Random Allocation
KW - Xenograft Model Antitumor Assays
KW - Irinotecan
KW - Quercetin/administration & dosage
KW - Animals
KW - Mice, Nude
KW - Cell Line, Tumor
UR - http://www.scopus.com/inward/record.url?scp=85032928522&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032928522&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2017.09.011
DO - 10.1016/j.jnutbio.2017.09.011
M3 - Article
C2 - 29125991
AN - SCOPUS:85032928522
SN - 0955-2863
VL - 51
SP - 105
EP - 113
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
ER -