Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer in vitro
Article Category: Research Article
Published Online: Nov 29, 2017
Page range: 407 - 414
Received: Jun 28, 2017
Accepted: Oct 13, 2017
DOI: https://doi.org/10.1515/raon-2017-0048
© 2017 Jakob Liermann, Patrick Naumann, Franco Fortunato, Thomas E. Schmid, Klaus-Josef Weber, Jürgen Debus, Stephanie E. Combs
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Chemoradiation of locally advanced non-metastatic pancreatic cancer can lead to secondary operability by tumor mass reduction. Here, we analyzed radiomodulating effects of oridonin and ponicidin in pancreatic cancer
Materials and methods
Pancreatic cancer cell lines AsPC-1, BxPC-3, Panc-1 and MIA PaCa-2 were pretreated with oridonin or ponicidin and irradiated with 2 Gy to 6 Gy. Long-term survival was determined by clonogenic assay. Cell cycle effects and intensity of γH2AX as indicator for DNA double-strand breaks were investigated by flow cytometry. Western blotting was used to study the DNA double-strand break repair proteins Ku70, Ku80 and XRCC4.
Results
Oridonin and ponicidin lead to a dose-dependent reduction of clonogenic survival and an increase in γH2AX. Combined with irradiation we observed additive effects and a prolonged G2/M-arrest. No relevant changes in the levels of the DNA double-strand break repair proteins were detected.
Conclusions
Pretreatment with oridonin or ponicidin followed by irradiation lead to an additional reduction in survival of pancreatic cancer cells