Escin inhibits angiogenesis by suppressing interleukin-8 and vascular endothelial growth factor production by blocking nuclear factor-kappa B activation in pancreatic cancer cell lines

摘要

Pancreatic cancer (PaCa) is one of the most aggressive types of cancer. Thus, the development of new and more effective therapies is urgently required. Escin, a pentacyclic triterpenoid from the horse chestnut, has been reported to exhibit antitumor potential by reducing cell proliferation and blocking the nuclear factor-kappa B (NF-kappa B) signaling pathway in several types of cancer. Our previous study reported that NF-kappa B enhanced the secretion of interleukin (IL)-8 and vascular endothelial growth factor (VEGF), thereby inducing angiogenesis in PaCa cell lines. In the present study, it was examined whether escin inhibited angiogenesis by blocking NF-kappa B activation in PaCa. It was initially confirmed that escin, at concentrations >10 mu M, significantly inhibited the proliferation of several PaCa cell lines. Next, using immunocytochemical staining, it was found that escin inhibited the nuclear translocation of NF-kappa B. Furthermore, ELISA confirmed that NF-kappa B activity in the escin-treated PaCa cells was significantly inhibited and reverse transcription-quantitative PCR showed that the mRNA expression levels of tumor necrosis factor-alpha-induced IL-8 and VEGF were significantly suppressed following escin treatment in the PaCa cell lines. ELISA also showed that escin decreased the secretion of IL-8 and VEGF from the PaCa cells. Furthermore, tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escin-treated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the secretion of IL-8 and VEGF by blocking NF-kappa B activity in PaCa. In conclusion, escin could be used as a novel molecular therapy for PaCa.