Study of regulating histone acetylizad level with VPA on the proliferation of breast cancer cells / 中国医师杂志

ABSTRACT

Objective To investigate the effect and the mechanism of up-regulating histone acetylizad level with a selective inhibitor of HDACs-Valproate acid sodium (VPA) on breast cancer cell proliferation. Methods MCF-7 cells were cultured with 0.75-4.0 mmol/L valproic acid (VPA) for 24, 48, 72, 96 hours in vitro, the inhibiting rate was tested by MTT assay. Cell cycle was analyzed by flow eytome- try with PI assay, and the protein and mRNA expressions of Cyelin A, Cyclin DI, Cyclin E, P21Waf/cipl of MCF-7 cells after 1.5, 3.0 mmol/ L VPA treated were analyzed by indirect immunofluorescence technique and RT-PCR respectively. Results After cultured with 0.75 -4.0 mmol/L valproic acid (VPA) for 24, 48, 72, 96 hours, the inhibiting rate of experimental groups increased significantly(P<0.01) and a dose and acting time dependent manner was found. As to cell cycle, the percentages of GI, S, M phrase in control groups remained the same. Contrary to control groups, 0. 75 -4.0 mmo]/L VPA induced a significant arrest in G1 phrase ( P<0.01), and a total of 55.4% -82.8% G1 phrase ratio were found. P21Waf/cipl was up-regulated both at the mRNA and protein level while Cyclin D1 was down-regulated ( P<0.001). Conversely, neither mRNA nor protein expression of Cyclin A, Cyclin E showed difference ( P>0.05). Conclusions Up- regulating histone acetylizad level can inhibit breast cancer cell proliferation, induce cell cycle arrest in G1 phrase. VPA, as a I class of histone deaeetylase inhibitor, can be used as an option in the treatment of breast cancer. The mechanism may include up-regulating P21Waf/cipl mRNA and protein expression and down-regulating Cyclin D1 mRNA and protein expression.