Original Paper

Journal of Cancer Research and Clinical Oncology

, Volume 138, Issue 5, pp 785-797

First online:

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

  • Yong-Wei WangAffiliated withDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University
  • , Shuang-Jia WangAffiliated withDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University
  • , Yi-Nan ZhouAffiliated withDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University
  • , Shang-Ha PanAffiliated withDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University
  • , Bei SunAffiliated withDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University Email author 

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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.

Keywords

Pancreatic cancer Escin Gemcitabine Nuclear factor-κB