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http://dx.doi.org/10.4333/KPS.2006.36.6.385

Penetration of Paclitaxel in Multicellular Layers of Human Colorectal Cancer Cells  

Choi, Mi-Sun (Department of Biomedical Sciences, College of Medicine, The Catholic Univ. of Korea)
Park, Jong-Kook (Department of Biomedical Sciences, College of Medicine, The Catholic Univ. of Korea)
AL-Abd Ahmed M. (Department of Biomedical Sciences, College of Medicine, The Catholic Univ. of Korea)
Kuh Hyo-Jeong (Department of Biomedical Sciences, College of Medicine, The Catholic Univ. of Korea)
Publication Information
Journal of Pharmaceutical Investigation / v.36, no.6, 2006 , pp. 385-392 More about this Journal
Abstract
Paclitaxel is an important chemotherapeutic agent for the treatment of human solid tumors. Multicellular resistance(MCR) is considered to be a major mechanism of resistance of human solid tumors to chemotherapeutic agent such as paclitaxel, which includes barriers to drug penetration through tumor tissues. Multicellular layers(MCL) cultures resemble in vivo tumor condition in terms of MCR and has been used successfully to produce clinically relevant data. In the present study, we evaluated the penetration characteristics and post-penetration anti-proliferative activity of paclitaxel using MCL of human colorectal cancer cells(DLD-1 and HT-29) grown in Transwell inserts. The penetration of $[^{14}C]-paclitaxel$ was slower than that of mannitol which penetrates via paracellular pathway in DLD-1 MCL. The penetration of $[^{14}C]-paclitaxel$ was faster in HT-29 MCL compared to DLD-1 MCL, i.e., at 10 ${\mu}M$ 100% and 40% penetration were observed after 48 hr incubation for HT-29 and DLD-1 cells, respectively. When calculated using anti-proliferative activity in the conditioned media of bottom chamber, the penetration after 24 hr was very limited(less than 50%) and concentration-dependent at the concentrations tested in both MCL's. These results suggest that limited and differential penetration of paclitaxel in tumor tissues may contribute to lower and differential efficacy against human solid tumors.
Keywords
Paclitaxel; Multicellular layers; Tissue penetration;
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