Chidamide and 5-flurouracil show a synergistic antitumor effect on human colon cancer xenografts in nude mice

Neoplasma
L LiuH Chen

Abstract

Chidamide is a novel histone deacetylase (HDAC) inhibitor that increases the acetylation of histone H3 by inhibiting the activity of HDAC1 and HDAC2. We previously found that treatment of human colon cancer cells with chidamide led to cell apoptosis and cell cycle arrest at G0/1 phase in vitro. The present study extended the observations in vivo and explored the underlying molecular mechanisms. In nude mice bearing human colon cancer LoVo cell xenografts, chidamide alone or in combination with 5-flurouracil (5-Fu) reduced the expression of HDAC1 and HDAC2, accompanied with increased acetylation of histone H3. Chidamide alone inhibited the tumor growth and induce cell apoptosis in tumor-bearing mice. Combined treatment of chidamide with 5-Fu enhanced the anti-tumor activity of 5-Fu. Western blotting analysis showed that chidamide alone or in combination with 5-Fu upregulated the expressions of cleaved Caspase-3 and cleaved poly-ADP (adenosine diphosphate)-ribose polymerase (PARP). In addition, chidamide alone or in combination with 5-Fu increased the p53, phosphorylated-p53 (p-p53), p21 and γH2AX levels, but suppressed cyclin dependent kinase 4 (CDK4) expression in tumor cells. Chidamide alone or in combination with 5-Fu down re...Continue Reading

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