Tanshinone IIA down-regulates heat shock protein 27 in pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine

Abstract

Background: The aim of this proteomic analysis was to investigate the effect of tanshinone IIA (a diterpenoid naphthoquinone extracted from the root of Salvia miltiorrhiza) on pancreatic cancer cells with poor prognosis such as chemoresistance in an attempt to elucidate the molecular mechanisms of the anti-cancer effects reported in the literature such as growth inhibition, apoptosis and differentiation induction in cancer cells.

Material and Methods: Gemcitabine (GEM)-resistant pancreatic cancer KLM1-R cells, treated with or without tanshinone IIA, were analysed by using two-dimensional gel electrophoresis (2-DE) and the spots which showed significantly different intensities were identified with mass spectrometry. The protein levels of identified spots were confirmed by Western blotting by using specific antibodies. The cytotoxic effects of the combinatorial treatment of GEM with tanshinone IIA was assessed by MTS assay.

Results: A number of protein spots showed significantly different intensities between tanshinone IIA-treated or untreated KLM1-R cells. Among them, heat shock protein 27 (HSP27) was confirmed to be down-regulated by tanshinone IIA. We had previously reported that down-regulation of HSP27 increased GEM-sensitivity in resistant pancreatic cancer cells, and have now shown that the combinatorial treatment of GEM with tanshinone IIA results in a significant synergistic cytotoxic effect on GEM-resistant KLM1-R cells.

Conclusions: Proteomic analysis for tanshinone IIA-treated pancreatic cancer cells showed a marked difference in the expression levels of some proteins including HSP27, and an increased sensitivity to GEM. Thus the combinatorial treatment of GEM with tanshinone IIA is expected to be an effective therapy for patients with GEM-resistant pancreatic cancer.