Clobenpropit enhances anti-tumor effect of gemcitabine in pancreatic cancer

doi:10.3748/wjg.v20.i26.8545

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jul 14, 2014; 20(26): 8545-8557
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8545

Clobenpropit enhances anti-tumor effect of gemcitabine in pancreatic cancer

Woo Hyun Paik, Ji Kon Ryu, Kyoung-Sin Jeong, Jin Myung Park, Byeong Jun Song, Sang Hyub Lee, Yong-Tae Kim, Yong Bum Yoon

Woo Hyun Paik, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Koyang 411-706, South Korea

Ji Kon Ryu, Kyoung-Sin Jeong, Jin Myung Park, Byeong Jun Song, Sang Hyub Lee, Yong-Tae Kim, Yong Bum Yoon, Division of Gastroenterology, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea

Author contributions: Paik WH performed the experiments and wrote the manuscript; Jeong KS performed the majority of the experiments; Ryu JK designed the study and revised the manuscript; Park JM and Song BJ performed the experiments; Lee SH, Kim YT and Yoon YB critically revised the manuscript.

Supported by Korean Society of Internal Medicine Research Fund (2012) and the Seoul National University College of Medicine Research Fund (2011)

Correspondence to: Ji Kon Ryu, MD, PhD, Associate Professor, Division of Gastroenterology, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea. jkryu@snu.ac.kr

Telephone: +82-2-20721962 Fax: +82-2-7436701

Received: December 1, 2013
Revised: February 27, 2014
Accepted: April 5, 2014
Published online: July 14, 2014

Core Tip

Core tip: Histamine is associated with carcinogenesis through activation of its 4 membrane-specific receptors. Clobenpropit, which is an agonist of H₄ receptor, inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine. Clobenpropit up-regulated an epithelial marker, but down-regulated mesenchymal markers in real-time polymerase chain reaction. In addition, clobenpropit inhibited tumor growth and enhanced apoptosis in combination with gemcitabine by up-regulation of E-cadherin and down-regulation of Zeb1 in Panc-1 xenograft mouse. In conclusion, clobenpropit enhanced anti-tumor effects of gemcitabine in pancreatic cancer cells through inhibition of epithelial-mesenchymal transition process.