Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Establishment of in vitro 3-Dimensional Tumor Model for Evaluation of Anticancer Activity Against Human Solid Tumors

항고형암제의 활성평가를 위한 in vitro 삼차원 암세포 배양계의 확립

  • Lee, Sang-Hak (Catholic Research Institutes of Medical Science, The Catholic Univ) ;
  • Lee, Joo-Ho (Catholic Research Institutes of Medical Science, The Catholic Univ) ;
  • Kuh, Hyo-Jeong (Catholic Research Institutes of Medical Science, The Catholic Univ)
  • 이상학 (가톨릭대학교 의과학연구원 임상연구지원센터 연구개발부) ;
  • 이주호 (가톨릭대학교 의과학연구원 임상연구지원센터 연구개발부) ;
  • 구효정 (가톨릭대학교 의과학연구원 임상연구지원센터 연구개발부)
  • Published : 2004.10.20
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Abstract

For the efficient determination of activity against solid tumors, an in vitro tumor model that resembles the condition of in vivo solid tumors, is required. The purpose of this study was to establish a rapid culture method and viability assay for an in vitro 3-dimensional tumor model, multicellular spheroid (MCS). Among 12 human cancer cell lines, a few cell lines including DLD-1 (human colorectal carcinoma cells) formed fully compact MCS which was adequate for in vitro viability assay. DLD-1 MCS showed steady growth reaching $700\;{\mu}m$ diameter after 11 day culture. DLD-1 cells grown as MCS showed significant increase in $G_0/G_1$ phase compared to the monolayer cells (73.9% vs 45.7%), but necrotic regions or apoptotic cells were not observed. The cells cultured as MCS showed resistance to 5-FU (10.3 fold higher $IC_{50}$) compared to monolayers, however, tirapazamine (a hypotoxin) showed similar activity in both culture systems. In summary, MCS may be a valid in vitro model for activity screening of anticancer agents against human solid tumors and also exploitable for studying molecular markers of drug resistance in human solid tumors.

Keywords

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