Effects of suramin on proliferation and apoptosis of hepatic stellate cells of hepatic fibrosis rats

doi:10.5246/jcps.2011.04.053

Abstract

Abstract:

The aim of the study was to investigate the role of suramin in the proliferation and apoptosis of activated hepatic stellate cells (HSCs). HSCs were cultured in medium with different doses of suramin. The cell proliferation rate was determined using methyl thiazolyl tetrazolium (MTT) assay. Both the cell cycle and proliferation index (PRI) were analyzed using flow cytometry. The apoptotic rate of HSCs was measured using TdT-mediated dUTP nick end labeling (TUNEL) method. The conformation of HSCs was observed using microscopy. The results indicated that the HSCs proliferation rate of suramin treated cells was significantly reduced compared to the control cells. After HSCs were treated with suramin for 72 h, the cell proliferation rate reached the lowest value compared to the control cells. Our results indicated that suramin inhibited the proliferation of HSCs in a time- and dose-dependent manner. After HSCs were treated with suramin for 24 h, the percentage of HSCs in the G1 phase exhibited a significant increase, the PRI showed a remarkable decrease, while the HSCs apoptosis rate did not show any obvious change. In addition, it seemed that suramin failed to affect the conformation of HSCs. Our data suggested that within the dose range used in the present study, suramin inhibited the proliferation of HSCs, but it could not induce HSCs apoptosis.

Key words: Suramin, Hepatic stellate cells, Proliferation, Apoptosis, Hepatic fibrosis

CLC Number:

R575.2

Supporting:

Xin Chen, He-Ming Xiu, Hui-Qing Jiang^*. Effects of suramin on proliferation and apoptosis of hepatic stellate cells of hepatic fibrosis rats[J]. , DOI: 10.5246/jcps.2011.04.053.

References

[1] Wang, J.Y.; Zhang, Q.S.; Guo, J.S.; Hu, M.Y. World J. Gastroenterol. 2001, 7, 115-119.
[2] Svegliati-Baroni, G.; Ridolfi, F.; Di Sario, A.; Saccomanno, S.; Bendia, E.; Benedetti, A. Hepatology. 2001, 33, 1130-1140.
[3] Pinzani, M. Pharmacol. Ther. 1995, 66, 387-412.
[4] Blomhoff, R.; Wake, K. FASEB J. 1991, 5, 271-277.
[5] Friedman, S.L. J. Biol. Chem. 2000, 275, 2247-2250.
[6] Hautekeete, M.L.; Geerts, A. Virchows Arch. 1997, 430, 195-207.
[7] Vasiliou, V.; Lee, J.; Pappa, A.; Petersen, D.R. Biochem. Biophys. Res. Commun. 2000, 273, 546-550.
[8] Kato, R.; Kamiya, S.; Ueki, M.; Yajima, H.; Ishii, T.; Nakamura, H. Exp. Cell Res. 2001, 265, 54-63.
[9] Lang, A.; Schoonhoven, R.; Tuvia, S.; Brenner, D.A.; Rippe, R.A. J. Hepatol. 2000, 33, 49-58.
[10] Liang, Y.; Jansen, M.; Aronow, B.; Geiger, H.; Van Zant, G. Nat. Genet. 2007, 39, 178-188.
[11] Iwamoto, H.; Sakai, H.; Tada, S.; Nakamuta, M.; Nawata, H. J. Lab. Clin. Med. 1999, 134, 83-89.
[12] Kisseleva, T.; Brenner, D.A. J. Gastroenterol. Hepatol. 2006, 3, S84-87.
[13] Fischer, R.; Schmitt, M.; Bode, J.G.; Haussinger, D. Gastroenterology. 2001, 120, 1212-1226.
[14] Issa, R.; Williams, E.; Trim, N.; Kendall, T.; Arthur, M.J.; Reichen, J. Gut. 2001, 48, 548-557.
[15] Zhong, Q.L.; Luo, H.S.; Zhang, J. Chin. J. Gastroenterol. Hepatol. 2009, 18, 907-910.
[16] Dranoff, J.A.; Ogawa, M.; Kruglov, E.A.; Gaca, M.D.; Sevigny, J.; Robson, S.C. Am. J. Physiol. Gastrointest. Liver Physiol. 2004, 287, G417-424.
[17] Kaur, M.; Reed, E.; Sartor, O.; Dahut, W.; Figg, W.D. Invest. New Drugs. 2002, 20, 209-219.
[18] Lossos, I.S.; Izbicki, G.; Or, R.; Goldstein, R.H.; Breuer, R. Life Sci. 2000, 67, 2873-2881.
[19] Zhong, Q.L.; Luo, H.S.; Zhang, J. Chin. J. Gastroenterol. Hepatol. 2009, 18, 907-910.
[20] Greenwel, P.; Schwartz, M.; Rosas, M.; Peyrol, S.; Grimaud, J.A.; Rojkind, M. Lab. Invest. 1991, 65, 644-653.
[21] Engisch, R.; Schurmann, K.; Bienert, H. J. Vasc. Interv. Radiol. 2000, 11, 639-644.
[22] Rieck, P.; Kriegsch, J.; Jaeckel, C. Ophthalmologe. 2004, 101, 73-79.
[23] Eichhorst, S.T.; Krueger, A.; Muerkoster, S.; Fas, S.C.; Golks, A.; Gruetzner, U. Nat. Med. 2004, 10, 602-609.
[24] Bitton, R.J.; Figg, W.D.; Venzon, D.J.; Dalakas, M.C.; Bowden, C.; Headlee, D. J. Clin. Oncol. 1995, 13, 2223-2229.
[25] Coffey, R.J.Jr.; Leof, E.B.; Shipley, G.D.; Moses, H.L. J. Cell Physiol. 1987, 132, 143-148.
[26] Hu, Y.; Zon, Y.; Dietrich, H.; Wick, G.; Xu, Q. Circulation. 1999, 100, 861-868.
[27] Cha, S.H.; Hahn, T.W.; Sekine, T.; Lee, K.H.; Endou, H. Jpn. J. Pharmacol. 2000, 82, 181-187.
[28] Li, C.; Jiang, X.; Yang, L.; Liu, X.; Yue, S.; Li, L. Am. J. Pathol. 2009, 175, 1464-1472.
[29] Li, C.; Kong, Y.; Wang, H.; Wang, S.; Yu, H.; Liu, X.; Yang, L.; Jiang, X.; Li, l.; Li, L. J. Hepatol. 2009, 50, 1174-1183.
[30] Li, C.; Zheng, S.; You, H.; Liu, X.; Lin, M.; Yang, L.; Li, L. J. Hepatol. 2011, 54, 1205-1213.
[31] Rieck, P.W.; Kriegsch, J.; Jaeckel, C.; Hartmann, C. Ophthalmologe. 2004, 101, 73-79.
[32] Zhu, X.B.; Tang, S.B.; Luo, Y.; Huang, X.K. Chin. J. Ophthalmol. 2005, 41, 110-113.
[33] Dranoff, J.A.; Ogawa, M.; Kruglov, E.A.; Gaca, M.D.; Sevigny, J.; Robson, S.C. Am. J. Physiol. Gastrointest. Liver Physiol. 2004, 287, G417-424.
[34] Dranoff, J.A.; Krugloy E.A.; Abreu-Lanfranco, O.; Nguven, T.; Arora, G.; Jain, D. In Vivo. 2007, 21, 957-965.
[35] Chen, X.; Jiang, H.Q.; Yang, L.T.; Wang, Y.Z.; Hu, C.X. Acta. Anat. Sin. 2006, 37, 66-68.
[36] Trim, N.; Morgan, S.; Evans, M.; Issa, R.; Fine, D.; Afford, S. Am. J. Pathol. 2000, 156, 1235-1243.