The Dual PI3K/mTOR Inhibitor NVP-BEZ235 Enhances the Antitumoral Activity of Gemcitabine in Human Pancreatic Cancer Cell LinesLuise Maute, Johannes Wicht and Lothar Bergmann*
Department of Internal Medicine II, Hematology and Oncology, University Hospital, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
- *Corresponding Author:
- Dr. Lothar Bergmann
Medizinische Klinik II (Hematology/Oncology)
Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany
Tel: +49 (0)69-6301-5121
E-mail: [email protected]
Received date: March 05, 2015; Accepted date: March 31, 2015; Published date: April 07, 2015
Citation: Maute L, Wicht J, Bergmann L (2015) The Dual PI3K/mTOR Inhibitor NVPBEZ235 Enhances the Antitumoral Activity of Gemcitabine in Human Pancreatic Cancer Cell Lines. J Integr Oncol 4:133. doi:10.4172/2329-6771.1000133
Copyright: © 2015 Maute L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors still
associated with poor prognosis in advanced stages. Gemcitabine is one of the standard agents for the treatment of
PDAC, without having a major impact on the clinical outcome. Combining two compounds acting via different ways
of action may result in a better efficacy.
Methods: We investigated the effects of gemcitabine in combination with the dual PI3k/mTOR inhibitor BEZ235
in four human pancreatic cancer cell lines (Panc-1, BxPC-3, MiaPaCa-2 and AsPC-1). The cells were analysed with
MTT assay for cell viability, FACS-analysis for cell cycle distribution. Real-time RT-PCR and Western blot for survivin/
BIRC5, STAT3, BCl-xL and WNT16 mRNA and protein expression and γH2AX.
Results: Application of NVP-BEZ235 or gemcitabine inhibited cell viability of AsPC-1 and BxPC-3 cells while
Panc-1 and MiaPaCa-2 remained nearly unaffected. Combined treatment of gemcitabine and BEZ235, however,
enhanced the inhibitory effect on cell viability of Panc-1 and MiaPaCa-2 cells of about 80% compared to control
cells. This effect was boosted by time-delayed application of the two compounds. The biggest impact on cell growth,
viability and downstream gene regulations were achieved by a sequential incubation with gemcitabine followed by
BEZ235 24 hours later.
Conclusions: Combining gemcitabine with dual PI3K/mTOR inhibitors like NVP-BEZ2235 improved the efficacy
on growth inhibition in human pancreatic cell lines especially by sequential application of both agents.