Gastric Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2004; 10(12): 1726-1729
Published online Jun 15, 2004. doi: 10.3748/wjg.v10.i12.1726
Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo
Da-Qiang Li, Zhi-Biao Wang, Jin Bai, Jie Zhao, Yuan Wang, Kai Hu, Yong-Hong Du
Da-Qiang Li, Zhi-Biao Wang, Jin Bai, Jie Zhao, Yuan Wang, Kai Hu, Yong-Hong Du, State Key Laboratory of Ultrasound Engineering in Medicine, Chongqing Medical University, Chongqing 400016, China
Author contributions: All authors contributed equally to the work.
Supported by the National Key Research Project Foundation of China, No.96-905- 02-01, and the National Natural Science Foundation of China, No. 39630340
Correspondence to: Dr. Zhi-Biao Wang, State Key Laboratory of Ultrasound Engineering in Medicine, Chongqing Medical University (PO Box 153), Chongqing 400016, China. wangzhibiao@netease.com
Telephone: +86-23-68485022 Fax: +86-23-68485023
Received: August 23, 2003
Revised: November 29, 2003
Accepted: December 6, 2003
Published online: June 15, 2004
Abstract

AIM: To investigate the effects of mifepristone on the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 and its mechanisms.

METHODS: After incubation with various concentrations of mifepristone (5, 10, 20 μmol/L), the adhesion to artificial basement membrane, Matrigel, and the migration of MKN-45 cells were assayed using MTT assay and Transwell cell culture chambers, respectively. Enzyme- linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine the expression of vascular endothelial growth factor (VEGF) and integrin β3 in the cells. After subcutaneous transplantation of MKN-45 cells in nude mice, mifepristone (50 mg/kg·d) was administrated subcutaneously for 8 wk to assess its effects on tumor metastasis. Immunohistochemical analysis was used to detect the expression of VEGF and microvascular density (MVD) in xenografted tumors.

RESULTS: Mifepristone dose-dependently inhibited the heterotypic adhesion to Matrigel of MKN-45 cells. The inhibition was accompanied by a significant down-regulation of integrin β3 expression in the cells. After incubation with 5, 10, 20 μmol/L mifepristone, the number of migrated MKN-45 cells was 72 ± 8, 50 ± 6, 41 ± 5 in experiment group, and 94 ± 16 in control group (P < 0.01). Meanwhile, secreted VEGF protein of MKN-45 cells in mifepristone-treated group (14.2 ± 2.9, 8.9 ± 3.1, 5.4 ± 2.1 ng/g per liter) was significantly lower than that in control group (22.7 ± 4.3 ng/g per liter, P < 0.01). In vivo, mifepristone decreased the number of metastatic foci in lungs of nude mice and down-regulated the expression of VEGF and MVD in the xenograted tumors.

CONCLUSION: Mifepristone can effectively inhibit the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo through inhibition of heterotypic adhesion to basement membrane, cell migration and angiogenesis.

Keywords: $[Keywords]