http://genesdev.cshlp.org/content/20/10/1353.short
and
J Cancer Res Clin Oncol. 2012 May;138(5):785-97. doi: 10.1007/s00432-012-1152-z. Epub 2012 Jan 24.
Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in pancreatic cancer both in vitro and in vivo.
Wang YW, Wang SJ, Zhou YN, Pan SH, Sun B.
Author information
Abstract
PURPOSE:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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.
PMID:
22270965
[PubMed - indexed for MEDLINE]
