Browse > Article
http://dx.doi.org/10.7314/APJCP.2013.14.2.747

Inhibition of Growth and Induction of Differentiation of SMMC-7721 Human Hepatocellular Carcinoma Cells by Oncostatin M  

Kong, N. (Department of Regenerative Medicine, College of Pharmacy, Jilin University)
Zhang, X.M. (Department of Regenerative Medicine, College of Pharmacy, Jilin University)
Wang, H.T. (Department of Regenerative Medicine, College of Pharmacy, Jilin University)
Mu, X.P. (Laboratory of Tang Ao-qing, China-Japan Union Hospital, Jilin University)
Han, H.Z. (Journal of Jilin University Medicine Edition, Jilin University)
Yan, W.Q. (Department of Regenerative Medicine, College of Pharmacy, Jilin University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.2, 2013 , pp. 747-752 More about this Journal
Abstract
Oncostatin M (OSM) is a multifunctional cellular regulator acting on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. Previous studies have shown that OSM can induce morphological and/or functional differentiation and maturation of many tumor cells. However, the action of OSM on the induction of differentiation of human hepatocellular carcinoma (HCC) has not been reported. Here, we investigated the effects of different concentrations of OSM on human HCC cell line SMMC-7721 growth, proliferation, cell cycling, apoptosis and differentiation in vitro. Cell growth was determined via MTT assay, proliferation by cell cycle analysis, apoptosis by flow cytometry, morphology by transmission electronic microscopy, and cell function by detection of biochemical markers. Our results demonstrated that OSM strongly inhibited the growth of SMMC-7721 cells in a dose-dependent manner, associated with decreased clonogenicity. Cell cycle analysis revealed a decreased proportion of cells in S phase, with arrest at G0/G1. The apotosis rate was increased after OSM treatment compared to the control. These changes were associated with striking changes in cellular morphology, toward a more mature hepatic phenotype, accompanied by significant reduction of the expression of AFP and specific activity of ${\gamma}$-GT, with remarkable increase in secretion of albumin and ALP activity. Taken together, our findings indicate that OSM could induce the differentiation and reduce cell viability of SMMC-7721 cells, suggesting that differentiation therapy with OSM offers the opportunity for therapeutic intervention in HCC.
Keywords
OSM; HCC; proliferation; apoptosis; differentiation;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Blais ME, Louis I, Perreault C (2006). T-cell development: an extrathymic perspective. Immunol Rev, 209, 103-14.   DOI   ScienceOn
2 Brounais B, David E, Chipoy C, et al (2009). Long term oncostatin M treatment induces an osteocyte-like differentiation on osteosarcoma and calvaria cells. Bone, 44, 830-9.   DOI   ScienceOn
3 Bruce AG, Hoggatt IH, Rose TM (1992). Oncostatin M is a differentiation factor for myeloid leukemia cells. J Immunol, 149, 1271-5.
4 Chen SH, Gillespie GY, Benveniste EN (2006). Divergent effects of oncostatin M on astroglioma cells: influence on cell proliferation, invasion, and expression of matrix metalloproteinases. Glia, 53, 191-200.   DOI   ScienceOn
5 Damdinsuren B, Nagano H, Kondo M, et al (2006). TGF-beta1-induced cell growth arrest and partial differentiation is related to the suppression of Id1 in human hepatoma cells. Oncol Rep, 15, 401-8.
6 Guan YS (2006). Hepatocellular carcinoma: the curative attempts. J US-China Med Sci, 3, 59-71.
7 Halfter H, Friedrich M, Resch A, et al (2006). Oncostatin M induces growth arrest by inhibition of Skp2, Cks1, and cyclin A expression and induced p21 expression. Cancer Res, 66, 6530-9.   DOI   ScienceOn
8 Hamada T, Sato A, Hirano T, et al (2007). Oncostatin M gene therapy attenuates liver damage induced by dimethylnitrosamine in rats. Am J Pathol, 171, 872-81.   DOI   ScienceOn
9 Hay DC, Zhao D, Fletcher J, et al (2008). Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells, 26, 894-902.   DOI   ScienceOn
10 Kamiya A, Gonzalez FJ, Nakauchi H (2006). Identification and differentiation of hepatic stem cells during liver development. Front Biosc, 11, 1302-10.   DOI
11 Kinoshita T, Miyajima A (2002). Cytokine regulation of liver development. Biochim Biophys Acta, 1592, 303-12.   DOI   ScienceOn
12 Kong N, Mu X, Han H, et al (2009). Pilot-scale fermentation, purification, and characterization of recombinant human oncostatin M in pichia pastoris. Protein Expr Purif, 63, 134-9.   DOI   ScienceOn
13 Kong WJ, Abidi P, Kraemer FB, et al (2005). In vivo activities of cytokine oncostatin M in regulation of plasma lipid levels. J Lipid Res, 46, 1163-71.   DOI   ScienceOn
14 Li WQ, Dehnade F, Zafarullah M (2001). Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol, 166, 3491-8.   DOI
15 Luyckx VA, Cairo LV, Compston CA, et al (2009). Oncostatin M pathway plays a major role in the renal acute phase response. Am J Physiol Renal Physiol, 296, 875-83.   DOI   ScienceOn
16 Masaki T, Shiratori Y, Rengifo W, et al (2003). Cyclins and cyclin-dependent kinases: comparative study of hepatocellular carcinoma versus cirrhosis. Hepatology, 37, 534-43.   DOI   ScienceOn
17 McCormick C, Freshney RI (2000). Activity of growth factors in the IL-6 group in the differentiation of human lung adenocarcinoma. Br J Cancer, 82, 881-90.   DOI   ScienceOn
18 Morikawa Y (2005). Oncostatin M in the development of the nervous system. Anat Sci Int, 80, 53-9.   DOI   ScienceOn
19 Okaya A, Kitanaka J, Kitanaka N, (2005). Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes. Am J Pathol, 166, 709-19.   DOI   ScienceOn
20 Sensken S, Waclawczyk S, Knaupp AS (2007). In vitro differentiation of human cord blood-derived unrestricted somatic stem cells towards an endodermal pathway. Cytotherap, 9, 362-78.   DOI   ScienceOn
21 Silver JS, Hunter CA ( 2010). gp130 at the nexus of inflammation, autoimmunity, and cancer. J Leukoc Biol, 88, 1145-56.   DOI   ScienceOn
22 Wang CT, Meng M, Zhang JC (2008). Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate. Chin Med J (Engl), 121, 1707-11.
23 Sims NA, Walsh NC (2010). GP130 cytokines and bone remodelling in health and disease. BMB Rep, 43, 513-23.   DOI   ScienceOn
24 Song HY, Jeon ES, Jung JS (2005). Oncostatin M induces proliferation of human adipose tissue-derived mesenchymal stem cells. Int J Biochem Cell Biol, 37, 2357-65   DOI   ScienceOn
25 Tanaka M, Miyajima A (2003). Oncostatin M, a multifunctional cytokine. Rev Physiol Biochem Pharmacol, 149, 39-52.
26 Wei X, Wang CY, Liu QP (2008). In vitro hepatic differentiation of mesenchymal stem cells from human fetal bone marrow. J Int Med Res, 36, 721-7.   DOI   ScienceOn
27 Weiss TW, Samson AL, Niego B, et al (2006). Oncostatin M is a neuroprotective cytokine that inhibits excitotoxic injury in vitro and in vivo. FASEB J, 20, 2369-71.   DOI   ScienceOn
28 West NR, Murphy LC, Watson PH (2012). Oncostatin M suppresses oestrogen receptor-$\alpha$ expression and is associated with poor outcome in human breast cancer. Endocr Relat Cancer, 19, 181-95.   DOI   ScienceOn
29 Yamashita Y, Shimada M, Harimoto N, et al (2003). Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells. Int J Cancer, 103, 572-6.   DOI   ScienceOn
30 Zekri AR, Hassan ZK, Bahnassy AA, et al (2012). Molecular prognostic profile of Egyptian HCC cases infected with hepatitis C virus. Asian Pac J Cancer Prev, 13, 5433-8.   DOI   ScienceOn
31 Zeng XL, Tu ZG (2003). In vitro induction of differentiation by Ginsenoside Rh2 in SMMC-7721 hepatocarcinoma cell line. Pharmacol Toxicol, 93, 275-83.   DOI   ScienceOn