Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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A New Bioluminescent Rat Prostate Cancer Cell Line: Rapid and Accurate Monitoring of Tumor Growth

효과적인 항암효능측정을 위한 발광 전립선 세포의 개발 및 평가

  • Lee, Mi-Sook (Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute) ;
  • Jung, Jae-In (Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute) ;
  • Kwon, Seung-Hae (Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute) ;
  • Shim, In-Sop (Department of Medical Science, Graduate School of East-West Medical Science Kyung Hee University) ;
  • Hahm, Dae-Hyun (Department of Medical Science, Graduate School of East-West Medical Science Kyung Hee University) ;
  • Han, Jeong-Jun (Glonet, Doosan Co.) ;
  • Han, Dae-Seok (Korea Food Research Institute) ;
  • Yoonpark, Jung-Han (Department of Food Science and Nutrition, Hallym University) ;
  • Her, Song (Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute)
  • 이미숙 (한국기초과학지원연구원 춘천센터) ;
  • 정재인 (한국기초과학지원연구원 춘천센터) ;
  • 권승해 (한국기초과학지원연구원 춘천센터) ;
  • 심인섭 (경희대학교 한의학연구소) ;
  • 함대현 (경희대학교 한의학연구소) ;
  • 한정준 (두산 글로넷) ;
  • 한대석 (한국식품연구원 식품자원이용연구본부) ;
  • 윤정한 (한림대학교 식품영양학과) ;
  • 허송욱 (한국기초과학지원연구원 춘천센터)
  • Received : 2010.09.27
  • Accepted : 2010.11.11
  • Published : 2010.11.30
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Abstract

Caliper measurements of tumor volume have been widely used in the assessment of tumors in animal models. However, experiments based on caliper data have resulted in unreliable estimates of tumor growth, due to necrotic areas of tumor mass. To overcome this systematic bias, we engineered a new luciferase-expressing rat prostate cancer cell line (MLL-Luc) that produces bioluminescence from viable cancer cells. MLL-Luc cells showed a strong correlation between bioluminescence intensity and cell number ($R^2$=0.99) and also accurately quantified tumor growth, with reduced bioluminescence signals caused by necrotic cells in a subcutaneous MLL-Luc xenograft model. The accurate quantification of tumor growth with bioluminescence imaging (BLI) was confirmed by a better antitumor effect of combination chemotherapy, compared to that based on caliper measurements with a correlation between the bioluminescence signal and tumor volume ($R^2$=0.84). These data suggest that bioluminescent MLL xenografts are a powerful and quantitative tool for monitoring tumor growth and are useful in evaluating the efficacy of anticancer drugs, with less systematic bias.

기존의 동물모델에서 암의 성장은 caliper를 이용하여 고형암 부피를 측정으로써 조사하였으나, 암 조직 속의괴사와 부종으로 인하여 부피측정에 신뢰성이 결여 되어 있다. 이러한 문제점을 해결하기 위해 발광 암세포를 이용하여 광학생체영상적으로 분석하는 방법이 개발 되었다. 본 연구에서는 전립선 발광 암세포를 제조하여 고형암 동물모델에서 B16 발광 암세포와 암 성장을 비교 측정하여 신규발광 암세포를 평가하였다. In vitro에서 세포 수와 발광강도는 높은 상관관계를 보였고($R^2$=0.99), 고형암 동물모델에서 암 성장 측정은 괴사에 의한 오차를 줄였다. 이러한 발광신호를 기반으로 한 측정방법은 caliper의 부피 측정에 비하여 높은 항암효과를 보임으로써 기존의 발광 암세포보다 신규 발광전립선 암세포의 유용성을 증명하였다.

Keywords

References

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