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KN-93, a Specific Inhibitor of CaMKII Inhibits Human Hepatic Stellate Cell Proliferation in Vitro

Ping An, Jun-Yong Zhu, Yan Yang, Peng Lv, Yi-Hao Tian, Ming-Kai Chen, He-Sheng Luo

World J Gastroenterol. 2007 Mar 7;13(9):1445-8.

PMID: 17457979

Abstract:

Aim:
To investigate the effects of KN-93, a CaMKII selective inhibitor on cell proliferation and the expression of p53 or p21 protein in human hepatic stellate cells.
Methods:
Human hepatic stellate cells (LX-2) were incubated with various concentrations (0-50 micromol/L) of KN-93 or its inactive derivative, KN-92. Cell proliferation was measured by CCK-8 assay, and the expression of two cell cycle regulators, p53 and p21, was determined by SDS-PAGE and Western blotting.
Results:
KN-93 (5-50 micromol/L) decreased the proliferation of human hepatic stellate cells in a dose-dependent manner from 81.76% (81.76% +/- 2.58% vs 96.63% +/- 2.69%, P < 0.05) to 27.15% (27.15% +/- 2.86% vs 96.59% +/- 2.44%, P < 0.01) after 24 h treatment. Incubation of 10 micromol/L KN-93 induced the cell growth reduction in a time-dependent manner from 78.27% at 8 h to 11.48% at 48 h. However, KN-92, an inactive derivative of KN-93, did not inhibit cell proliferation effectively. Moreover, analysis of cell cycle regulator expression revealed that KN-93 rather than KN-92 reduced the expression of p53 and p21.
Conclusion:
KN-93 has potent inhibitory effect on proliferation of LX-2 cells by modulating the expression of two special cell cycle regulators, p53 and p21.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP139298401-B KN-93 KN-93 139298-40-1 Price
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