Selective Inhibition of Histone Deacetylases 1/2/6 in Combination with Gemcitabine: A Promising Combination for Pancreatic Cancer Therapy
Abstract
:1. Introduction
2. Results
2.1. Inhibition of Multiple HDACs Is Required for the Effects of HDAC Inhibitors on PDAC Cells
2.2. Inhibition of HDACs 1, 2, and 6 Accounts for the Effects of HDAC Inhibitors in PDAC Cells
2.3. Pharmacological Inhibition of HDACs 1, 2, and 6 Synergizes with Gemcitabine in PDAC Cells
2.4. Selective Inhibition of HDACs 1, 2, and 6 Increases the Apoptosis-Inducing Effects of Gemcitabine In Vitro and Augments the Antitumor Effects of Gemcitabine In Vivo
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Western Blot Analysis
4.3. MTT Assay
4.4. siRNA Knockdown
4.5. Annexin V-FITC assay
4.6. Mouse Xenograft Studies
4.7. Analysis of Drug Interactions
4.8. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Laschanzky, R.S.; Humphrey, L.E.; Ma, J.; Smith, L.M.; Enke, T.J.; Shukla, S.K.; Dasgupta, A.; Singh, P.K.; Howell, G.M.; Brattain, M.G.; et al. Selective Inhibition of Histone Deacetylases 1/2/6 in Combination with Gemcitabine: A Promising Combination for Pancreatic Cancer Therapy. Cancers 2019, 11, 1327. https://doi.org/10.3390/cancers11091327
Laschanzky RS, Humphrey LE, Ma J, Smith LM, Enke TJ, Shukla SK, Dasgupta A, Singh PK, Howell GM, Brattain MG, et al. Selective Inhibition of Histone Deacetylases 1/2/6 in Combination with Gemcitabine: A Promising Combination for Pancreatic Cancer Therapy. Cancers. 2019; 11(9):1327. https://doi.org/10.3390/cancers11091327
Chicago/Turabian StyleLaschanzky, Richard S., Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, and et al. 2019. "Selective Inhibition of Histone Deacetylases 1/2/6 in Combination with Gemcitabine: A Promising Combination for Pancreatic Cancer Therapy" Cancers 11, no. 9: 1327. https://doi.org/10.3390/cancers11091327