Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Effect of ω3-Fatty Acid Desaturase Gene Expression on Invasion and Tumorigenicity in Human Tongue Squamous Cell Carcinoma Cells

인체 혀의 편평세포암 세포에서 ω3-fatty acid desaturase 유전자 발현이 침윤 및 종양형성에 미치는 영향

  • Hong, Tae-Hwa (Department of Biochemisty, College of Medicine, Chungnam National University) ;
  • Shin, Soyeon (Department of Biochemisty, College of Medicine, Chungnam National University) ;
  • Han, Seung-Hyeon (Department of Biochemisty, College of Medicine, Chungnam National University) ;
  • Hwang, Byung-Doo (Department of Biochemisty, College of Medicine, Chungnam National University) ;
  • Lim, Kyu (Department of Biochemisty, College of Medicine, Chungnam National University)
  • 홍태화 (충남대학교 의과대학 생화학교실) ;
  • 신소연 (충남대학교 의과대학 생화학교실) ;
  • 한승현 (충남대학교 의과대학 생화학교실) ;
  • 황병두 (충남대학교 의과대학 생화학교실) ;
  • 임규 (충남대학교 의과대학 생화학교실)
  • Received : 2018.04.06
  • Accepted : 2018.05.08
  • Published : 2018.08.30
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Abstract

Omega-3 polyunsaturated fatty acids (${\omega}3$-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ${\omega}3$-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ${\omega}3$ fatty acids, a stable SCC-9 cell line expressing the ${\omega}3$-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ${\omega}3$ fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.

오메가-3 지방산(오메가-3)은 수종의 암에 대해 종양형성 억제 및 침윤이 억제됨이 알려져 있다. 그러나 혀의 편평세포암 세포에서 내인성 오메가-3에 의한 침윤 및 종양형성 억제 대한 연구가 명확하게 보고된 바 없다. 이에 본 연구는 혀의 편평세포암 세포에서 ${\omega}3$-fatty acid desaturase의 유전자 발현이 침윤 및 종양형성에 미치는 영향을 규명하였다. 먼저 SCC-4 및 SCC-9세포의 침윤능은 오메가-3인 DHA 처리에 의해 억제 됨을 확인 하였다. DHA 처리 후 MMP-9 및 MMP-2 활성이 감소 되었을 뿐만 아니라 그 promoter의 reporter 활성도 억제하였다. 또한 COX-2 및 VEGF promoter 활성 뿐만 아니라 NF-kB 활성도 DHA에 의해 억제 되었다. SCC-9의 ${\omega}3$-desaturase 유전자 stable 세포(fSCC-9sc)의 세포증식 및 colony formation이 억제 되었으며, in vivo 동물실험에서 fSCC-9sc 세포의 종양형성능은 현저히 억제 되었고, 면역형광염색법을 이용한 fSCC-9sc 세포의 종양 조직에서의 TUNEL 양성세포는 대조군인 fSCC-9cc 세포에 비해 현저히 증가하였다. 이상의 결과로 오메가-3는 인체 혀의 편평세포암 세포의 침윤 뿐만 아니라 종양형성을 억제하여 항암작용을 나타낼 수 있으며 따라서 오메가-3는 인체 혀의 편평암의 예방 및 치료에 유용하게 사용될 수 있으리라 생각된다.

Keywords

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