Department of Experimental Evolutive Biology, University of Bologna, Bologna, Italy.
Anticancer Res. 2012 Jul;32(7):2855-62.
In this study, we investigated the antiproliferative and anti-invasive mechanism action of sodium valproate (VPA), an inhibitor of histone deacetylase (HDAC) activity, in combination with the rexinoid 6-OH-11-O-hydroxyphenanthrene (IIF), a ligand of retinoid X receptor (RXR), in the HT-29 and LoVo colon cancer cell lines. VPA inhibited HDAC-1 and increased RXRγ expression. VPA and IIF reduced viability in a dose- and time-dependent manner. The combined use of VPA and IIF enhanced the apoptosis induction. In particular, the BCL2 level decreased, while levels of BAX, cleaved caspase-3 and caspase-9 increased. The same treatment also reduced invasiveness of HT-29 cell line through the inhibition of metalloproteinase-9 (MMP9) expression, and MMP9 and MMP2 activity, with an increase of tissue inhibitors of MMPs TIMP1 and TIMP2. In conclusion, VPA and IIF have strong proapoptotic and anti-invasive effects in the HT-29 colon cancer cell line and their effects are enhanced when used together.
在这项研究中，我们研究了组蛋白去乙酰化酶 (HDAC) 活性抑制剂丙戊酸钠 (VPA) 与视黄酸 X 受体 (RXR) 配体 6-OH-11-O-羟基菲（IIF）联合使用对 HT-29 和 LoVo 结肠癌细胞系的抗增殖和抗侵袭机制作用。VPA 抑制 HDAC-1 并增加 RXRγ 表达。VPA 和 IIF 呈剂量和时间依赖性降低细胞活力。联合使用 VPA 和 IIF 增强了细胞凋亡诱导。特别是 BCL2 水平下降，而 BAX、cleaved caspase-3 和 caspase-9 水平增加。同样的治疗还通过抑制基质金属蛋白酶-9 (MMP9) 的表达和 MMP9 和 MMP2 的活性来降低 HT-29 细胞系的侵袭性，同时增加基质金属蛋白酶抑制剂 TIMP1 和 TIMP2 的水平。总之，VPA 和 IIF 在 HT-29 结肠癌细胞系中具有很强的促凋亡和抗侵袭作用，当联合使用时效果增强。
