Investigating the antitumor activity of pnu-74654 as wnt/β-catenin inhibitor, alone or in combination with gemcitabine in miapaca-2 pancreatic cancer cell

Sajjad Sharifi,1,* Amir avan,2

Abstract

Introduction

Wnt/beta-catenin pathway is one of the key dysregulated pathways in several malignancies, including pancreatic cancer (pc). the aim of current study was to explore the anticancer activity of pnu-74654, as a wnt/ β-catenin inhibitor, in pancreatic cancer cells, alone and in combination with gemcitabine in 2 and 3 dimentional cell culture model.

Methods

The viability of the pc cells was determined using mtt assay, while the cytotoxicity of this agent was evaluated in 3 dimensional cell culture model (spheroid). the expression levels of candidate genes involved in wnt/b-catenin pathway was evaluated at mrna by rt-pcr.

Results

Pnu-74654 suppressed cell growth at ic50 value of 122±0/4 umol/l and synergistically enhanced the antiproliferative activity of gemcitabine via modulation of wnt pathway

Conclusion

We demonstrated the antitumor activity of pnu-74654 in pancreatic cancer, supporting further investigations on the therapeutic potential of this novel anticancer agent in in vivo models.

Keywords

Pancreatic cancer, pnu-74654, wnt pathway, gemcitabine