생명과학회지 (Journal of Life Science)

  • 제15권6호
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  • Pages.895-903
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  • 2005
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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Helixor A는 시험관 내에서 thrombospondin-1의 상승조절을 통해 신혈관생성을 억제한다.

Helixor A Inhibits Angiogenesis in vitro Via Upregutation of Thrombospondin-1

  • 염동훈 (가톨릭대학교 의과대학 생화학교실) ;
  • 홍경자 (가톨릭대학교 의과대학 생화학교실)
  • Yeom Dong-Hoon (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Hong Kyong-Ja (Department of Biochemistry, College of Medicine, The Catholic University of Korea)
  • 발행 : 2005.12.01
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초록

Thrombospondin-1은 암성장과 신혈관생성 억제조절인자로 병리학적 조건과 세포외에서의 자극에 의해 세포 특이적으로 조절되어지고 이 TSP-1 유전자 발현조절은 암치료제 개발을 위한 새로운 접근으로 중요하다. Mistletoe는 기생식물로 면역조절과 항암제로 사용되어지고 있다. Helixor A는 mistletoe 추출물의 수용액부분이다. 여기서 우리는 Helixor A를 투여하면 간암세포주 (Hep3B)와 혈관내피세포주 (BAE)에서 TSP-1의 mRWA와 단백질 발현이 유도되는 것을 관찰하였다. TSP-1 promoter 활성분석으로 TSP-1유전자의 발현이 Helixor A에 의해 전사단계에서 조절되어 진다는 것을 확인하였다. 세포 침윤 분석에서 Helixor A를 처리한 배지를 두 세포주에 처리함으로 침윤된 세포의 수가 현저하게 줄어드는 것을 관찰하였고, Matrigel에서 혈관 내피 세포 (BAE)의 모세관 형성을 억제하는 것을 관찰하였다. 또한 세포 침윤과 모세관 형성에서 Helixor A를 처리했던 배지의 억제 효과가 TSP-1 중화 항체에 의해 그 효과가 상실되었다. 그러므로, 이 결과는 TSP-1이 Helixor A에 의해 유도되어진 혈관신생 억제 효과에 연관이 있음을 제시하였다. 이러한 결과를 종합 하였을 때 Helixor A가 TSP-1의 상승조절을 통해 혈관신생 억제 효과를 가질 것이라고 생각된다.

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated under pathological conditions or by extracellular stimuli, and the regulation of TSP-1 gene expression is important for developing new approaches in tumor therapy. Mistletoe is a parasitir plant that have been used for immunomodulation and antitumor therapy. Helixor A is an aqueous part of mistletoes extract. Here we showed that TSP-1 expression was significantly induced at both mRNA and protein levels in the Hepatocarcinorna cell line (Hep3B) and primary bovine endothelial cell line (BAE) exposed to Helixor A. Our promoter analysis confirmed that the expression of TSP-1 gene was regulated by Helixor A at the transcriptional level. In cell invasion assay, the conditioned media obtained from treatment of these cells significantly reduced the number of invasive cells and also inhibited capillary-like tube formation of BAE cells on Matrigel. Moreover, the inhibitory efforts of the conditioned media on cell invasion and tube formation were reversed by blocking with anti-TSP-1 neutralizing antibodies, suggesting that TSP-1 is involved in Helixor A-indured antiangiogenic effect. Taken together, our results suggest that Helixor A have an antiangiogenic effects through upregulation of TSP-1.

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