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A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance

Authors
 Hee Seung Lee  ;  Soo Been Park  ;  Sun A Kim  ;  Sool Ki Kwon  ;  Hyunju Cha  ;  Do Young Lee  ;  Seonggu Ro  ;  Joong Myung Cho  ;  Si Young Song 
Citation
 SCIENTIFIC REPORTS, Vol.7 : 41615, 2017 
Journal Title
 SCIENTIFIC REPORTS 
Issue Date
2017
Abstract
Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future.
Files in This Item:
T201700339.pdf Download
DOI
10.1038/srep41615
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sun A(김선아) ORCID logo https://orcid.org/0000-0002-7174-3640
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154322
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