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

• DOI: 10.1038/srep41615
• Publication Date: 2017-01-30T11:45:33Z
• 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
• Keywords: Histone deacetylase inhibitor; Erlotinib Hydrochloride

Abstract Pancreatic cancer is predominantly lethal, and primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors emerging therapeutic agents, since HDAC plays an important role in initiation progression. We evaluated the antitumor effect of a inhibitor, CG200745, combined gemcitabine/erlotinib on pancreatic cells gemcitabine-resistant cells. Three cancer-cell lines were used evaluate CG200745 gemcitabine/erlotinib. induced expression apoptotic proteins (PARP caspase-3) increased levels acetylated histone H3. showed significant growth inhibition synergistic effects vitro. In vivo , reduced size up 50%. enhanced decreased level ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) MRP4. The had anti-tumor significantly improved prominent clinical outcome expected future.