Anti-invasive Effects and Proapoptotic Activity Induction by the Rexinoid IIF and Valproic Acid in Combination on Colon Cancer Cell Lines

作者：Papi A; Ferreri A M^*; Guerra F; Orlandi M

来源：Anticancer Research, 2012, 32(7): 2855-2862.

• Valproic acid
• histone deacetylase inhibitors
• matrix metalloproteinases
• rexinoid
• apoptosis
• anti-invasive effects
• colon cancer cell lines
• IIF

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-I and increased RXR gamma 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.

• 出版日期2012-7