VPA inhibits breast cancer cell migration by specifically targeting HDAC2 and down-regulating Survivin
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Cell migration plays major roles in human breast cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers including breast cancer. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human breast cancer MDA-MB-231 cells. Mechanistic studies found that VPA significantly inhibited the expression of Survivin. Knockdown of Survivin could obviously inhibited cell migration, while over-expression of Survivin markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on Survivin and cell migration, and over-expression of Survivin could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that HDAC2 may be the specific target of VPA in breast cancer cells, and specific inhibition of HDAC2, especially by small molecular chemicals may lead to less side-effects and provide a better strategy than VPA application for human breast cancer treatment.
KeywordsBreast cancer Migration Valproic acid HDAC2 Survivin
This study was supported by grants from the National Natural Science Foundation of China (90919028, 31071306, 31101061, and 30971451), Ministry of Science and Technology (2011CB965100, 2010CB944900, 2010CB945000, 2011CBA01100, and 2011DFA30480), Science and Technology Commission of Shanghai Municipality (09DZ2260100, 11ZR1438500, 11XD1405300), and Program for Young Excellent Talents in Tongji University (2009KJ089).
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