Non-nuclear localization of Ki-67 in human colorectal cancer cells grown as multicellular layers

Yu Jin Kim, Sang Hoon Lee, Jaehwi Lee, Hyo Jeong Kuh

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Multicellular layers (MCL) of cancer cells is an in vitro 3-dimensional (3D) model that mimics avascular microregions of human solid tumors and has been shown to be useful in pharmacokinetic-pharmacodynamic studies of anticancer agents. We investigated whether Ki-67, which is widely used as a proliferation marker, can be used to evaluate changes in proliferative fractions following drug exposure in MCL of HT-29 human colorectal cancer cells. Ki-67 expression was monitored and compared between cancer cells cultured as monolayers or MCL. Drug distribution and Ki-67 expression were evaluated within MCL following exposure to doxorubicin and paclitaxel. Ki-67 expression was observed in the nuclei of proliferating cells in monolayers, tumor xenograft, and multicellular spheroids. In MCL, however, Ki-67 expression was detected in the membrane/cytoplasm as well as in the nucleus throughout MCL. Neither the location nor the level of expression changed following drug exposure, whereas drug-induced apoptosis increased. Our data show that membranous/cytoplasmic Ki-67 may not be valid as a marker for the proliferative activity of cells grown as MCL. Studies for non-nuclear localization and its mechanism in 3D in vitro models of other cell lines are warranted.

Original languageEnglish
Pages (from-to)634-640
Number of pages7
JournalArchives of pharmacal research
Issue number5
Publication statusPublished - 2013 May


  • HT-29 human colorectal cancer cells
  • Ki-67
  • Multicellular layer
  • Multicellular spheroid
  • Proliferation marker
  • Three-dimensional culture

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry


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