|
KMID : 0369820060360060385
|
|
Jorunal of Korean Pharmaceutical Sciences
2006 Volume.36 No. 6 p.385 ~ p.392
|
|
|
Penetration of Paclitaxel in Multicellular Layers of Human Colorectal Cancer Cells
|
|
Choi Mi-Sun
Park Jong-Kook
Ahmed M.AL-Abd
Kuh Hyo-jeong
|
|
|
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 cacer cells(DLD-1 and HT-29) grown in Traswell inserts. The penetration of [14C]-paclitaxel was slower than that of mannitol which penetrates via paracellualr pathway in DLD-1 MCL. The penetration of [14C]-paclitaxel was fater in HT-29 MCL compared to DLD-1 MCL, I,e., at 10μM 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 peneration after 24hr was very limited (less that 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.
|
|
|
KEYWORD
|
|
|
Paclitaxel in Multicellular layers, Tissue penetration
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|