PMID- 26774139
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20190128
IS  - 0028-2685 (Print)
IS  - 0028-2685 (Linking)
VI  - 63
IP  - 2
DP  - 2016
TI  - Chidamide and 5-flurouracil show a synergistic antitumor effect on human colon 
      cancer xenografts in nude mice.
PG  - 193-200
LID - 10.4149/203_150422N214 [doi]
AB  - 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 gammaH2AX levels, but suppressed cyclin dependent 
      kinase 4 (CDK4) expression in tumor cells. Chidamide alone or in combination with 
      5-Fu down regulated the expressions of p-AKT, p-mammalian target of rapamycin 
      (mTOR), p-p70S6K, p-Raf, and p44/42 mitogen activated protein kinase (Erk1/2), 
      indicating the blockage of these signaling pathways. The results demonstrated 
      that chidamide alone or in combination with 5-Fu exerted anti-tumor activity in 
      nude mice bearing human colon cancer LoVo cell xenografts, and several signaling 
      pathways might be involved in the chidamide-induced tumor growth inhibition and 
      tumor cell apoptosis.
FAU - Liu, L
AU  - Liu L
FAU - Qiu, S
AU  - Qiu S
FAU - Liu, Y
AU  - Liu Y
FAU - Liu, Z
AU  - Liu Z
FAU - Zheng, Y
AU  - Zheng Y
FAU - Su, X
AU  - Su X
FAU - Chen, B
AU  - Chen B
FAU - Chen, H
AU  - Chen H
LA  - eng
PT  - Journal Article
PL  - Slovakia
TA  - Neoplasma
JT  - Neoplasma
JID - 0377266
RN  - 0 (Aminopyridines)
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Benzamides)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 87CIC980Y0 
      (N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.5.1.98 (Hdac1 protein, mouse)
RN  - EC 3.5.1.98 (Hdac2 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Aminopyridines/*pharmacology
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/drug effects
MH  - Benzamides/*pharmacology
MH  - Caspase 3/metabolism
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Colonic Neoplasms/*drug therapy/*pathology
MH  - Fluorouracil/*pharmacology
MH  - Histone Deacetylase 1/antagonists & inhibitors
MH  - Histone Deacetylase 2/antagonists & inhibitors
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Histones/drug effects
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Poly (ADP-Ribose) Polymerase-1/metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - 5-flurouracil.
OT  - HDAC inhibitor
OT  - chidamide
OT  - colon cancer
EDAT- 2016/01/18 06:00
MHDA- 2019/01/29 06:00
CRDT- 2016/01/18 06:00
PHST- 2016/01/18 06:00 [entrez]
PHST- 2016/01/18 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
AID - 10.4149/203_150422N214 [doi]
PST - ppublish
SO  - Neoplasma. 2016;63(2):193-200. doi: 10.4149/203_150422N214.