title: Snail-1 regulates VDR signaling and inhibits 1,25(OH)-D₃ action in osteosarcoma.
abstract: 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 SaOS₂ cell line as in vitro model to study the effect of 1,25(OH)-D₃, 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)-D₃ on the expression of β-catenin signaling pathways were also studied. Then in vivo antiproliferative effect of 1,25(OH)-D₃ was also detected in nude mice injected with either mock-infected or Snail-1 SaOS₂ 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)-D₃ in osteosarcoma cells, and induce apoptosis and lower invasion in vitro. The effect of 1,25(OH)-D₃ was also associated with decreased expression of β-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/β-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)-D₃ as an anti osteosarcoma treatment.
authors.affiliation: Department of Orthopaedics, Afﬁliated Jiangyin Hospital of Southeast University, Wuxi 214400, PR China. yanghg5643@163.com
authors.forename: Huiguang
authors.initials: H
authors.lastname: Yang
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Jiang
authors.forename: Aidong
authors.initials: A
authors.lastname: Shen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D002117:Calcitriol