Arsenic trioxide (As2O3) inhibits peritoneal invasion of ovarian carcinoma cells in vitro and in vivo

Objectives. To study the role of arsenic trioxide (As2O3) in regulating peritoneal invasive activity of ovarian carcinoma cells in vitro and in vivo. Methods. The effects of As2O3 on human ovarian cancer cell lines (3AO, SW626 and HO-8910PM) migration, invasion and adhesion with tumor cells and human peritoneal mesothelial cells (HPMC) were observed by means of cell migration test, cell invasion test and cell adhesion test. The effects of As2O3 on MMP-2, MMP-9, TIMP-1 and TIMP-2 gene expressions and protein expressions of tumor cells were determined by RT-PCR and ELISA, respectively. In animal experiments, ovarian tumor cells were implanted into abdominal cavity of nude mice and then the nude mice were treated by intraperitoneal injection of different doses As2O3. The foci on the surface of peritoneum were counted. Results. As2O3 inhibited tumor cells migration, invasion and adhesion with HPMC in a dose-dependent manner, while the same treatment enhanced tumor cell-tumor cell interactions. As2O3 inhibited mRNA and protein expressions of MMP-2, MMP-9 and TIMP-2 of tumor cells. In contrast, As2O3 increased mRNA and protein expressions of TIMP-1. As2O3 could reduce tumor cells peritoneal metastasis in nude mice. Conclusion. As2O3 inhibits in vitro and in vivo peritoneal invasive activity of ovarian carcinoma cells in a dose-dependent manner. Its anti-invasive activity may be the results of reduced cell motility, inhibited attachment of tumor cells to HPMC and enhanced tumor cell-tumor cell interaction, as well as down-regulation of MMP-2 and MMP-9 levels and up-regulation of TIMP-1 level. (c) 2006 Elsevier Inc. All rights reserved.