KML001 Inhibits Cell Proliferation and Invasion in Pancreatic Cancer Cells through Suppression of NF-kappa B and VEGF-C

Abstract

Pancreatic cancer is an aggressive malignancy with poor prognosis and the efficacy of chemotherapy is limited. KML001 (sodium meta-arsenite) has been demonstrated to have anticancer activity against some solid cancer cells. The aim of the present study was to determine the effect of KML001 on cell proliferation, migration, and invasion of pancreatic cancer cells. The Dojindo Cell Counting Kit-8 assay was used to determine the inhibition of pancreatic cancer cell proliferation by drugs. Cell migration and invasion were examined using 24-well inserts and Matrigel (TM)-coated invasion chambers. The activity of nuclear factor-kappa B (NF-kappa B) p65, vascular endothelial growth factor-C (VEGF-C), and matrix metalloproteinase-9 (MMP-9) were measured by enzyme-linked immunosorbent assay (ELISA). KML001 inhibited the proliferation of pancreatic cancer cells in a dose-and time-dependent manner. KML001 also inhibited the migration and invasion of pancreatic cancer cells in a dose-dependent manner. KML001 significantly decreased NF-kappa B p65 and VEGF-C activities in the pancreatic cancer cells. KML001 inhibited cell proliferation, migration, and invasion in pancreatic cancer cells. Suppression of NF-kappa B and VEGF-C activation may partly be associated with the anticancer activity of KML001. These results suggest that KML001 could be a novel potential therapeutic agent for treatment of pancreatic cancer.