KSBB Journal

The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Effect of Simvastatin on the Migration and Invasion of U-373-MG Cells

U-373-MG 세포의 이동 및 침윤에 미치는 simvastatin의 효과

  • Kim, Hwan-Gyu (Division of Biological Sciences, Chonbuk National University)
  • 김환규 (전북대학교 자연과학대학 생물과학부)
  • Received : 2010.03.15
  • Accepted : 2010.06.22
  • Published : 2010.06.30
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Abstract

Simvastatins are widely used to reduce endogenous cholesterol synthesis and improve hypercholesterolemia. Also, simvastatin have been shown to induce both angiogenic and angiostatic responses. In this study, It was attempted to resolve this controversy by studying the effects of simvastatin on the cell migration and invasion with the proteinases secretion and expression pattern. U-373-MG cells treated with low dose of simvastatin ($0.001{\sim}0.5\;{\mu}M$) showed the induction of migration and invasion compared with the addition of a control buffer. On the contrary, high dose of simvastatin ($1{\sim}20\;{\mu}M$) showed the reduction of migration and invasion compared with the addition of a control buffer. It was also showed that simvastatin-regulated migrative and invasive phenotypes were consistent with the secretion and expression pattern of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasmin.

본 연구에서는 simvastatin에 의한 U-373-MG 세포의 이동 및 침윤에 미치는 효과와 그 가능한 기작에 대해 조사하였다. U-373-MG 세포의 이동에 미치는 simvastatin의 효과를 확인한 결과, $0.01\;{\mu}M$의 simvastatin에서는 U-373-MG 세포의 이동이 약 43% 증가되었으나 $1\;{\mu}M$과 $20\;{\mu}M$에서는 세포의 이동이 각각 28%와 35% 억제되었다. 세포의 침윤 역시 $0.001\;{\mu}M$의 simvastatin에서는 23%, $0.01\;{\mu}M$에서는 26%의 침윤 증가가 관찰되었으나, $1\;{\mu}M$과 $10\;{\mu}M$에서는 세포의 침윤이 각각 45%와 54%가 억제되었다. $0.001\;{\mu}M$ 과 $0.01\;{\mu}M$의 simvastatin 처리에 의해 MMP-2의 분비량이 각각 30%와 59% 증가되었으나, $10\;{\mu}M$과 $20\;{\mu}M$의 simvastatin 처리에 의해 MMP-2의 분비량은 각각 31%와 60% 감소되었다. MMP-9 및 플라스민의 분비에 미치는 simvastatin의 효과도 MMP-2에 미치는 효과와 유사하였다. Simvastatin이 MMP-2와 MMP-9 단백질의 생성에 미치는 효과를 조사한 결과, $0.001{\sim}1\;{\mu}M$의 simvastatin에서는 MMP-2와 MMP-9 생성이 증가되었으나 $10{\sim}20\;{\mu}M$에서는 MMP-2와 MMP-9의 생성이 감소되었다. 이러한 결과는 낮은 농도의 simvastatin은 혈관신생을 유도하고 높은 농도의 simvastatin은 혈관신생을 억제한다는 것을 보여주는 것이다.

Keywords

References

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