Arsenic trioxide (As(2)O(3)) inhibits peritoneal invasion of ovarian carcinoma cells in vitro and in vivo.
OBJECTIVE
To study the role of arsenic trioxide (As(2)O(3)) in regulating peritoneal invasive activity of ovarian carcinoma cells in vitro and in vivo.


METHODS
The effects of As(2)O(3) 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 As(2)O(3) 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 As(2)O(3). The foci on the surface of peritoneum were counted.


RESULTS
As(2)O(3) inhibited tumor cells migration, invasion and adhesion with HPMC in a dose-dependent manner, while the same treatment enhanced tumor cell-tumor cell interactions. As(2)O(3) inhibited mRNA and protein expressions of MMP-2, MMP-9 and TIMP-2 of tumor cells. In contrast, As(2)O(3) increased mRNA and protein expressions of TIMP-1. As(2)O(3) could reduce tumor cells peritoneal metastasis in nude mice.


CONCLUSIONS
As(2)O(3) 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.
Zhang
Jingjing
J
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China. xzmzjj@163.com
Wang
Bo
B
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D010534:Peritoneal Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077237:Arsenic Trioxide