Epigenetic modification suppresses proliferation, migration and invasion of urothelial cancer cell lines

Brockmeyer,Phillipp; Hemmerlein,Bernhard

doi:10.3892/ol.2016.4877

Epigenetic modification suppresses proliferation, migration and invasion of urothelial cancer cell lines

Authors:
- Phillipp Brockmeyer
- Bernhard Hemmerlein
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Affiliations: Department of Oral and Maxillofacial Surgery, University Medical Centre Göttingen, Göttingen D‑37075, Germany, Department of Pathology, University Medical Centre Göttingen, Göttingen D‑37075, Germany
Published online on: July 18, 2016 https://doi.org/10.3892/ol.2016.4877
Pages: 1693-1700
Copyright: © Brockmeyer et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epigenetic approaches offer additional therapeutic options, including apoptosis induction, modification of cell cycle regulating proteins and the re‑expression of pharmaceutical targets, such as hormone receptors. The present study analyzed the effect of the epigenetic modifiers 5-aza-2'-deoxycytidine and Trichostatin A on the proliferative, migratory and invasive behavior of four urinary bladder cancer cell lines (RT‑4, RT‑112, VMCUB‑1 and T‑24), and the expression of various matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Cell proliferation, migration and invasion assays revealed that treatment with the two epigenetic modifiers resulted in proliferation inhibition in all cell lines, and migration and invasion inhibition in RT‑4, RT‑112 and T‑24 cell lines. Quantitative polymerase chain reaction demonstrated that the mRNA expression of a broad selection of MMPs and their TIMPs was induced in all cell lines, and MMP‑14 mRNA expression was suppressed in all cell lines, with the exception of RT-4. In conclusion, epigenetic modifications suppressed the motility and invasiveness of three out of four urothelial cancer cell lines. The inhibitory effect on cell motility appears to be crucial for reduced invasive properties. However, even a broad spectrum of mRNA analysis does not sufficiently explain the loss of invasiveness, as it does not allow for functional conclusions. Further complex urothelial tumour models should be applied to investigate whether epigenetic therapeutic approaches may be an option in urothelial cancer.

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