PMID- 21963453
OWN - NLM
STAT- MEDLINE
DCOM- 20120227
LR  - 20220330
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 670
IP  - 2-3
DP  - 2011 Nov 30
TI  - Snail-1 regulates VDR signaling and inhibits 1,25(OH)-D(3) action in osteosarcoma.
PG  - 341-6
LID - 10.1016/j.ejphar.2011.09.160 [doi]
AB  - Previous research has shown that vitamin D could suppress proliferation, 
      migration and invasion of cancers, but the effects of vitamin D may be related to 
      the expression of Snail-1, which could inhibit the expression of the vitamin-D 
      gene receptor (VDR). Snail-1 is overexpressed in osteosarcoma, this study was 
      conducted to determine whether inhibiting Snail-1 could increase the role of 
      vitamin D as an anti- osteosarcoma agent. We used stable transfection of the 
      SaOS(2) cell line as in vitro model to study the effect of 1,25(OH)-D(3), which is 
      the most active metabolite of vitamin D. The in vitro antiproliferative, 
      pro-apoptotic and inhibiting of invasion effects were examined. The effects of 
      1,25(OH)-D(3) on the expression of beta-catenin signaling pathways were also studied. 
      Then in vivo antiproliferative effect of 1,25(OH)-D(3) was also detected in nude 
      mice injected with either mock-infected or Snail-1 SaOS(2) cells. We found that 
      inhibition of Snail-1 signaling by transfection could increase the expression of 
      VDR, enhance the anti-proliferative activity of 1,25(OH)-D(3) in osteosarcoma 
      cells, and induce apoptosis and lower invasion in vitro. The effect of 
      1,25(OH)-D(3) was also associated with decreased expression of beta-catenin signaling, 
      which is related to VDR signaling. In vivo, the effect of antiproliferative was 
      higher in mice injected with either Snail-1-infected cells than with 
      mock-infected cells. Our findings suggest that canonical Snail-1/VDR/beta-catenin 
      signaling reflects an important underlying mechanism of osteosarcoma progression. 
      Therefore, strategies to suppress Snail-mediated signaling may lead to the better 
      action of 1,25(OH)-D(3) as an anti osteosarcoma treatment.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Yang, Huiguang
AU  - Yang H
AD  - Department of Orthopaedics, Af fi liated Jiangyin Hospital of Southeast University, 
      Wuxi 214400, PR China. yanghg5643@163.com
FAU - Zhang, Yunqing
AU  - Zhang Y
FAU - Zhou, Zhengming
AU  - Zhou Z
FAU - Jiang, Xuefeng
AU  - Jiang X
FAU - Shen, Aidong
AU  - Shen A
LA  - eng
PT  - Journal Article
DEP - 20110922
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antineoplastic Agents)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (SNAI1 protein, human)
RN  - 0 (Snai1 protein, mouse)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Calcitriol/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects/genetics
MH  - Humans
MH  - Mice
MH  - Osteoblasts/cytology/drug effects/metabolism
MH  - Osteosarcoma/*pathology
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Calcitriol/*metabolism
MH  - *Signal Transduction/drug effects/genetics
MH  - Snail Family Transcription Factors
MH  - Transcription Factors/deficiency/genetics/*metabolism
MH  - beta Catenin/metabolism
EDAT- 2011/10/04 06:00
MHDA- 2012/03/01 06:00
CRDT- 2011/10/04 06:00
PHST- 2011/03/01 00:00 [received]
PHST- 2011/09/06 00:00 [revised]
PHST- 2011/09/11 00:00 [accepted]
PHST- 2011/10/04 06:00 [entrez]
PHST- 2011/10/04 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
AID - S0014-2999(11)01143-5 [pii]
AID - 10.1016/j.ejphar.2011.09.160 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2011 Nov 30;670(2-3):341-6. doi: 10.1016/j.ejphar.2011.09.160. 
      Epub 2011 Sep 22.