Inhibition of human smooth muscle cell proliferation by Gamigeonsim-tang through the transcriptional regulation of cell cycle-controlling genes

The effects of Gamigeonsim-tang (GGT) on cellular proliferation and express ion of cell cycle-related genes were investigated in human smooth muscle ce ll HISM. HISM cells were treated with an aqueous extract of GGT. Cellular p roliferation was investigated by an immunocytometric analysis of PCNA expre ssion and a flow cytometric analysis of the cell cycle progression. Reduced expression of PCNA and a significant accumulation of GI phase cells were o bserved following treatment, indicating that GGT inhibits cellular prolifer ation of human smooth muscle cells. To explore whether GGT affects the tran scription of cell cycle-regulating genes, we evaluated mRNA expression of p 53, p21(Waf1), PCNA, Cyclin DI, Cdc2, Histone H3, c-Myc, and c-Fos using a quantitative RT-PCR analysis. While increased expressions of two negative c ell cycle regulators, p53 and p21(waf1) were found, reduced expressions of cell cycle stimulators, PCNA, c-Fos, and c-Myc, were identified following t reatment. Taken together, our study demonstrates that GGT inhibits cellular proliferation of human smooth muscle cell through the up- and down-regulat ion of growth-inhibiting and growth-promoting genes, respectively.