Journal
WORLD JOURNAL OF SURGICAL ONCOLOGY
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1477-7819-10-270
Keywords
u-PA inhibitor; Amiloride; Peritoneal metastasis; Gastric cancer
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Background: Peritoneal metastasis in gastric cancer represents a ubiquitous human health problem but effective therapies with limited side effects are still lacking. Although previous research suggested that u-PA was involved in some tumor metastasis such as lung-specific metastasis, the role of u-PA for peritoneal metastasis in gastric cancer is still unclear. The aim of this study was to explore whether selective pharmacological blockade of u-PA is able to affect the peritoneal metastasis of gastric cancer both in vivo and in vitro. Methods: In the present study, we evaluated the effects and explored the anti-tumor mechanisms of amiloride, a selective u-PA inhibitor, on a panel of gastric cancer cell lines and in a murine model of human gastric cancer MKN45. Results: The study showed that amiloride significantly inhibited the tumor growth and prolonged the survival of the tumor-bearing mice. In vitro, compared with controls, amiloride could not only significantly down-regulate the mRNA expression and protein level of u-PA from MKN45 cells with dose dependence but also inhibit the adhesion of HMrSV5 cells, migration and invasion of MKN45 cells. Conclusions: The findings in our current report provide evidence that selective u-PA inhibitor amiloride has potent effects against peritoneal metastasis in gastric cancer, suggesting its possible therapeutic value for the treatment of gastric cancer.
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