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

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473834.do
DOI
10.1038/srep41615
Title
A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growthand overcomes gemcitabine resistance
Description
This research was supported by a grant of the Korea Health TechnologyR&D Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea(grant number: HI14C1324).
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.
provenance
Made available in Cube on 2018-09-28T10:30:04Z (GMT). No. of bitstreams: 0
language
English
author
Lee, Hee Seung
Park, Soo Been
Kim, Sun A.
Kwon, Sool Ki
Cha, Hyunju
Lee, Do Young
Ro, Seonggu
Cho, Joong Myung
Song, Si Young
accessioned
2018-09-28T10:30:04Z
available
2018-09-28T10:30:04Z
issued
2017
citation
Scientific Reports(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473834.do
Funder
보건복지부
Funding Program
연구중심병원육성
Project ID
1465023083
Jurisdiction
Rep.of Korea
Project Name
The development of targeted therpies for the GI tumor-related cancer stem cell
rights
openAccess
type
article


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