Dong Xi-Feng, Song Qiang, Li Li-Zhen, Zhao Chuan-Li, Wang Lu-Qun
Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
Neuro Endocrinol Lett. 2007 Dec;28(6):775-80.
The expression of vascular endothelial growth factor receptor 1(VEGFR-1) in human multiple myeloma KM3 cells in vitro, effects of valproic acid (VPA), as a histone deacetylase inhibitor, on cell proliferation and apoptosis and the underlying molecular mechanism were investigated. The effects of VPA on the growth of KM3 cells were studied by MTT assay. The apoptosis rate was determined with flow cytometry. The mRNA level of VEGFR was determined by RT-PCR; and immunocytochemistry was used to detect the protein level of ac-H4 and VEGFR. VPA inhibited proliferation of KM3 cells in a time- and dose-dependent manner. Treatment with VPA (4, 2, 1 and 0.5 mmol/L) for 48h, the apoptosis rates of KM3 cells were (13.27+/-3.54)%, (22.13+/-1.20)%, (24.41+/-2.23)% and(40.62+/-4.28)% respectively. The expression of VEGFR-1 in KM3 cells were decreased in VPA-treated group by the immunochemistry and RT-PCR, whereas the acetylated histone H4(ac-H4) accumulated. It suggested VPA could decrease the expression of VEGFR-1 in KM3 cells, and it might play an important role in regulating the proliferation and apoptosis of multiple myeloma cell line KM3 cells. These results provide the framework for clinical trials.
研究了血管内皮生长因子受体1（VEGFR-1）在人多发性骨髓瘤KM3细胞中的体外表达、组蛋白去乙酰化酶抑制剂丙戊酸（VPA）对细胞增殖和凋亡的影响及其潜在分子机制。采用MTT法研究VPA对KM3细胞生长的影响。用流式细胞术测定凋亡率。通过RT-PCR测定VEGFR的mRNA水平；采用免疫细胞化学法检测乙酰化组蛋白H4（ac-H4）和VEGFR的蛋白水平。VPA以时间和剂量依赖性方式抑制KM3细胞的增殖。用VPA（4、2、1和0.5 mmol/L）处理48小时，KM3细胞的凋亡率分别为（13.27±3.54）%、（22.13±1.20）%、（24.41±2.23）%和（40.62±4.28）%。免疫化学和RT-PCR结果显示，VPA处理组中KM3细胞VEGFR-1的表达降低，而乙酰化组蛋白H4（ac-H4）积累。这表明VPA可降低KM3细胞中VEGFR-1的表达，可能在调节多发性骨髓瘤细胞系KM3细胞的增殖和凋亡中起重要作用。这些结果为临床试验提供了框架。
