Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Anti-Proliferative Effects of Selenium in HT-29 Colon Cancer Cells via Inhibition of Akt

HT-29 대장암세포에서 Akt 활성 저해에 따른 셀레늄의 세포 증식억제 효과

  • Park, Song-Yi (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University) ;
  • Kim, In-Seop (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University) ;
  • Lee, Se-Hee (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University) ;
  • Lee, Sol-Hwa (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University) ;
  • Jung, Da-Woon (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University) ;
  • Park, Ock-Jin (Department of Food and Nutrition, College of Life Science and Nano Technology, Hannam University) ;
  • Kim, Young-Min (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University)
  • 박송이 (한남대학교 생명나노과학대학 생명과학과) ;
  • 김인섭 (한남대학교 생명나노과학대학 생명과학과) ;
  • 이세희 (한남대학교 생명나노과학대학 생명과학과) ;
  • 이솔화 (한남대학교 생명나노과학대학 생명과학과) ;
  • 정다운 (한남대학교 생명나노과학대학 생명과학과) ;
  • 박옥진 (한남대학교 생명나노과학대학 식품영양학과) ;
  • 김영민 (한남대학교 생명나노과학대학 생명과학과)
  • Received : 2011.10.18
  • Accepted : 2011.12.29
  • Published : 2012.01.30
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Abstract

Akt is known to play an important role in cell proliferation and differentiation, and is also over-expressed in several types of cancer cells. In this study, we explored the anti-proliferative effects of selenium in HT-29 colon cancer cells, mediated through effects on Akt and COX-2. Selenium treatments at different concentrations and for different durations inhibited proliferation of HT-29 colon cancer cells and increased apoptotic cell death. Selenium treatment decreased Akt phosphorylation and COX-2 expression. Treatment with LY294002 (an Akt inhibitor) decreased proliferation of HT-29 cells, while a combined treatment with LY294002 and selenium resulted in even further decreases in cell proliferation. Inactivation of Akt by Akt siRNA treatment abolished these inhibitory effects on cell growth. COX-2 expression decreased in Akt transfected cells compared to non-transfected cells. These results suggest that selenium induced both anti-proliferative and apoptotic effects by inhibiting Akt phosphorylation and COX-2 expression. Selenium treatment also appeared to induce synergistic anti-proliferative effects by inhibition of Akt in HT-29 colon cancer cells.

Akt는 세포의 증식과 분화에 관여하며 많은 암종에서 과발현되어 있다는 것이 보고되었다. 본 연구에서는 Akt의 조절을 통한 셀레늄의 HT-29 세포의 세포증식억제 시너지효과를 확인하였다. 셀레늄을 농도별과 시간별로 처리하였을 때 HT-29 세포의 증식이 억제되었고, apoptosis가 일어남을 확인하였다. 셀레늄을 농도별로 처리하여 Western blotting 및 immunofluorescence를 실시한 결과 Akt의 인산화가 저해되었고 COX-2의 발현도 저해되었다. 또한 Akt 저해제인 LY294002를 처리한 결과, HT-29 대장암세포의 증식이 억제되었으며, LY294002를 셀레늄과 병행처리하였을 때 셀레늄에 의한 세포증식억제 효과가 더 강하게 나타나는 것을 확인하였다. Akt siRNA에 의한 Akt의 불활성화는 non-transfected 세포에 비하여 HT-29 세포의 성장을 더 강하게 억제하였으며, Akt가 불활성화 되었을 때 COX-2의 발현 역시 non-transfected 세포에 비하여 감소된 것을 확인하였다. 따라서 HT-29 세포에서 셀레늄의 세포증식억제 효과는 Akt와 COX-2 신호분자의 조절을 통해 일어나며, Akt 의 저해는 셀레늄의 대장암세포증식 억제에 시너지 효과를 나타냄을 확인하였다.

Keywords

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