title: All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions in vitro.
abstract: OBJECTIVE
  All-trans retinoic acid (ATRA) has been demonstrated to inhibit tumor growth by restoration of gap junctional intercellular communication (GJIC) via upregulation of connexin (Cx) expression in some solid tumors. However, the relationship between ATRA and GJIC remains unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the effect of ATRA on the GJIC function of OSCC.
  
  
  METHODS
  We measured the effects of ATRA on the viability and cell cycle distribution of SCC9 and Tca8113 OSCC cells. The GJIC function was observed using the scrape-loading dye transfer technique, and the mRNA and protein levels of Cx32 and Cx43 were detected by qRT-PCR, Western blot, and immunofluorescence assays.
  
  
  RESULTS
  ATRA inhibited the growth of OSCC cells in a dose- and time-dependent manner (P <0.05) and caused cell cycle arrest. ATRA-treated cells showed a 2.69-fold and 2.06-fold enhancement of GJIC in SCC9 and Tca8113 cells, respectively (P <0.05). Moreover, ATRA induced upregulation of Cx32 and Cx43 at both the mRNA and protein levels in OSCC cells.
  
  
  CONCLUSIONS
  Our results indicated that restoration of GJIC via enhanced Cx32 and Cx43 expression might serve as a novel mechanism for the anti-tumor effect of ATRA in OSCC.
authors.affiliation: Department of Oral Medicine, The Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Dai
authors.forename: Yulei
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.forename: Juan
authors.initials: J
authors.lastname: Xia
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects*; D018031:Connexin 43 / Q000096:biosynthesis*; D017630:Connexins / Q000096:biosynthesis*; D017629:Gap Junctions / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000097002:Gap Junction beta-1 Protein
chemical_list: D000970:Antineoplastic Agents; D018031:Connexin 43; D017630:Connexins; D012333:RNA, Messenger; D014212:Tretinoin; D000097002:Gap Junction beta-1 Protein