beta-escin and Pancreatic-Neoplasms

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‑κB (NF‑κB) signaling pathway in several types of cancer. Our previous study reported that NF‑κB 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‑κB activation in PaCa. It was initially confirmed that escin, at concentrations >10 µM, significantly inhibited the proliferation of several PaCa cell lines. Next, using immunocytochemical staining, it was found that escin inhibited the nuclear translocation of NF‑κB. Furthermore, ELISA confirmed that NF‑κB 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‑α‑induced

Topics: Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Escin; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Pancreatic Neoplasms; Transcription Factor RelA; Vascular Endothelial Growth Factor A

Pancreatic cancer is an aggressive malignancy, which generally develops resistance to chemotherapy. Agents that are safe and can sensitize cancer to chemotherapy are urgently needed. Escin, a natural mixture of triterpene saponins isolated from Aesculus wilsonii Rehd, has been demonstrated to possess anti-cancer activity both in vitro and in vivo. The anti-cancer activity of escin could be, in part, due to the inactivation of nuclear factor-κB (NF-κB). In contrast, chemotherapy including gemcitabine could activate NF-κB and lead to chemoresistance. Here, for the first time, we investigated whether escin, via the inactivation of NF-κB, would potentiate the antitumor activity of gemcitabine in pancreatic cancer.. Cell viability and proliferation, apoptosis, NF-κB activity and the expression of NF-κB-linked genes were all examined in vitro. The antitumor effect of escin with or without gemcitabine in pancreatic cancer was also assessed using BxPC-3 xenografts subcutaneously established in BALB/c nude mice.. Escin not only potentiated the proliferation-inhibiting and apoptosis-inducing effect of gemcitabine in both BxPC-3 and PANC-1 cell lines in vitro, but also dramatically enhanced its suppressive effect on tumor growth in nude mice. The mechanism is at least partially due to the inhibition of NF-κB activity and consequent inhibition of c-Myc, COX-2, Cyclin D1, Survivin, Bcl-2 and Bcl-xL, and the activation of caspase-3.. These data suggest that escin, via inactivation of NF-κB, could potentiate the efficacy of gemcitabine in combating pancreatic cancer, which could be a novel and potentially important therapeutic approach for the treatment for pancreatic cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Deoxycytidine; Down-Regulation; Drug Synergism; Escin; Gemcitabine; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Biological; NF-kappa B; Pancreatic Neoplasms; Tumor Cells, Cultured; Xenograft Model Antitumor Assays