Abstract |
Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [ suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls ( DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.
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Authors | Johana M Susanto, Emily K Colvin, Mark Pinese, David K Chang, Marina Pajic, Amanda Mawson, C Elizabeth Caldon, Elizabeth A Musgrove, Susan M Henshall, Robert L Sutherland, Andrew V Biankin, Christopher J Scarlett |
Journal | International journal of oncology
(Int J Oncol)
Vol. 46
Issue 5
Pg. 2223-30
(May 2015)
ISSN: 1791-2423 [Electronic] Greece |
PMID | 25695794
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Vorinostat
- Decitabine
- Azacitidine
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Azacitidine
(analogs & derivatives, pharmacology)
- Blotting, Western
- Cell Death
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Decitabine
- Disease Models, Animal
- Female
- Histone Deacetylase Inhibitors
(pharmacology)
- Humans
- Hydroxamic Acids
(pharmacology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Pancreatic Neoplasms
(pathology)
- Vorinostat
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