Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jan 14, 2010; 16(2): 193-200
Published online Jan 14, 2010. doi: 10.3748/wjg.v16.i2.193
Hepatopoietin Cn suppresses apoptosis of human hepatocellular carcinoma cells by up-regulating myeloid cell leukemia-1
Jing Chang, Yang Liu, Dong-Dong Zhang, Da-Jin Zhang, Chu-Tse Wu, Li-Sheng Wang, Chun-Ping Cui
Jing Chang, Dong-Dong Zhang, Da-Jin Zhang, Chu-Tse Wu, Li-Sheng Wang, Chun-Ping Cui, Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China
Yang Liu, Chu-Tse Wu, School of Chemical Engineering and Technology, Tianjin University, Weijin Road #92, Nankai District, Tianjin 300072, China
Author contributions: Chang J, Liu Y and Zhang DD contributed equally to this work and performed the majority of experiments; Zhang DJ, Wang LS and Wu CT provided the vital reagents and analytical tools and were also involved in editing the manuscript; Cui CP designed the study and wrote the manuscript.
Supported by (in part) Grants From the National Natural Science Foundation of China, No. 30800558 and No. 30930041 and the Chinese Major Special Science & Technology Project for Development of Major New Drugs, No. 2009ZX09103-617
Correspondence to: Dr. Chun-Ping Cui, Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China. cui_chunping2000@yahoo.com.cn
Telephone: +86-10-68158312 Fax: +86-10-68158311
Received: October 19, 2009
Revised: November 23, 2009
Accepted: November 30, 2009
Published online: January 14, 2010
Abstract

AIM: To investigate the role of hepatopoietin Cn (HPPCn) in apoptosis of hepatocellular carcinoma (HCC) cells and its mechanism.

METHODS: Two human HCC cell lines, SMMC7721 and HepG2, were used in this study. Immunostaining, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/HPPCn receptor in SMMC7721 and HepG2. Apoptotic cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide.

RESULTS: The HPPCn was highly expressed in human HCC cells and secreted into culture medium (CM). FITC-labeled recombinant human protein (rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9% to 85.6% and 88.4%, respectively (P < 0.05). HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin A. Additionally, HPPCn could up-regulate the expression of myeloid cell leukemia-1 (Mcl-1) in HCC cells via mitogen-activated protein kinase (MAPK) and sphingosine kinase-1.

CONCLUSION: HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.

Keywords: Hepatopoietin Cn; Autocrine; Hepatocellular carcinoma; Apoptosis; Myeloid cell leukemia-1