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KMID : 0606920060140020090
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Biomolecules & Therapeutics
2006 Volume.14 No. 2 p.90 ~ p.95
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Pharmacodynamics of CKD-602 (Belotecan) in 3D Cultures of Human Colorectal Carcinoma Cells
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Lee Sin-Hyung
Kim Joon-Kyum
Kuh Hyo-jeong
Park Jong-Kook
Cha Jung-Ho
Ahn Soon-Kil
Ahmed M. AL-ABD
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Abstract
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CKD-602exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vitro. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-1 human colorectal cancer cells, respectively, The maximum effects (Emax) induced by CKD-602 were sig- nificantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the IC50’s of CKD-602 decreased to 23.5±1.0nM in monolayers after 24-h exposure and 42.3±1.7 nM in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.
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KEYWORD
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CKD-602, Belotecan, Pharmacodynamics, Multicellular spheroid, Multicellular layer, solid tumor, penetration
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