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KMID : 0043320130360050634
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Archives of Pharmacal Research
2013 Volume.36 No. 5 p.634 ~ p.640
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Non-nuclear localization of Ki-67 in human colorectal cancer cells grown as multicellular layers
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Kim Yu-Jin
Lee Sang-Hoon
Lee Jae-Hwi
Kuh Hyo-Jeong
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Abstract
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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.
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KEYWORD
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Three-dimensional culture, Multicellular layer, Multicellular spheroid, Ki-67, Proliferation marker, HT-29 human colorectal cancer cells
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