Journal of Pharmaceutical Investigation

  • 제36권1호
  • /
  • Pages.1-9
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  • 2006
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  • 2093-5552(pISSN)
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  • 2093-6214(eISSN)
한국약제학회 (The Korean Society of Pharmaceutical Sciences and Technology)
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다층 배양된 암세포에서 파크리탁셀의 항증식효과 분석

Anti-proliferative Effect of Paclitaxel in Multicellular Layers of Human Cancer Cells

  • 강춘모 (가톨릭대학교 의과대학 생명의과학과) ;
  • 이주호 (가톨릭대학교 의과대학 생명의과학과) ;
  • 차정호 (가톨릭대학교 의과대학 해부학교실) ;
  • 구효정 (가톨릭대학교 의과대학 생명의과학과)
  • Kang, Choon-Mo (Department of Biomedical Sciences, College of Medicine, The Catholic Univ.) ;
  • Lee, Joo-Ho (Department of Biomedical Sciences, College of Medicine, The Catholic Univ.) ;
  • Cha, Jung-Ho (Department of Anatomy, College of Medicine, The Catholic Univ.) ;
  • Kuh, Hyo-Jeong (Department of Biomedical Sciences, College of Medicine, The Catholic Univ.)
  • 발행 : 2006.02.20
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초록

Human solid tumors exhibit a multicellular resistance (MCR) resulting from limited drug penetration and decreased sensitivity of tumor cells when interacting with their microenvironments. Multicellular cultures represent solid tumor condition in vivo and provide clinically relevant data. There is little data on antitumor effect of paclitaxel (PTX) in multicellular cultures although its MCR has been demonstrated. In the present study, we evaluated antiproliferative effects of PTX in multicellular layers (MCL) of DLD-1 human colorectal carcinoma cells. BrdU labeling index (LI), thickness of MCL, cell cycle distribution and cellular uptake of calcein were measured before and after exposure to PTX at 0.1 to 50 ${\mu}M$ for 24, 48 and 72 hrs. BrdU LI and thickness of MCL showed a concentration- and time-dependent decrease and the changes in both parameters were similar, i.e., 34.2% and 40.6% decrease in BrdU LI and thickness, respectively, when exposed to $50\;{\mu}M$ for 72 hr. The DLD-1 cells grown in MCL showed increase in $%G_{0}/G_{1}$ and resistance to cell cycle arrest and apoptosis compared to monolayers. Calcein uptake in MCL did not change upon PTX exposure, indicating technical problems in multicellular system. Overall, these data indicate that antitumor activity of PTX may be limited in human solid tumors (a multicellular system) and MCL may be an appropriate model to study further pharmacodynamics of PTX.

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