Histone deacetylase 6 selective inhibitor ACY1215 inhibits cell proliferation and enhances the chemotherapeutic effect of 5-fluorouracil in HCT116 cells.

BACKGROUND

ACY1215 is a selective histone deacetylase 6 (HDAC6) inhibitor, and can suppress tumor growth for many human cancers. However, its role in colon cancer and its impact on the chemotherapeutic effect of 5-fluorouracil (5-Fu) are largely unknown. The aim of the present study is to explore the effect of ACY1215 on cell growth, migration, invasion and apoptosis, along with its impact on the chemotherapeutic effect of 5-Fu in HCT116 cells.

METHODS

HCT116 cells were treated with ACY1215 with or without 5-Fu, and cell viability, proliferation, migration, invasion and apoptosis were explored.

RESULTS

The cell viability, colony formation number, wound closure rate, and migrated cell numbers of HCT116 cells significantly decreased, while the apoptotic cells significantly increased with the increased concentration of ACY1215 (P<0.05). The combination of ACY1215 and 5-Fu was more potent than either drug alone, as indicated by an increase of apoptotic cells, and by a decrease of cell viability, colony formation number, wound closure rate and migrated cell numbers. The expression of phosphorylated mitogen-activated protein kinases (pMEK) and phosphorylated extracellular-signal regulated protein kinase (pERK) were decreased when HCT116 cells were cultured with ACY1215.

CONCLUSIONS

Selective HDAC6 inhibitor, ACY1215, could inhibit the cell proliferation, migration and invasion, and induce apoptosis of HCT116 colon cancer cells. Furthermore, ACY1215 may enhance the chemotherapeutic effect of 5-Fu in HCT116 cells.