ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

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P4. EFFICIENCY AND TRANSPORT OF TAXANES IN HUMAN BREAST CANCER CELLS
Marie Ehrlichova 1 , Radka Vaclavikova 1 , Katerina Kloudova 1,2 , Veronika Brynychova 1,2 ,
Vlasta Nemcova 3 , Jana Voborilova 3 , Stanislav Horsky 1 , Iwao Ojima 4 , Ivan Gut 1 and Pavel
Soucek 1
1
Laboratory of Toxicogenomics, National Institute of Public Health in Prague, Czech
Republic; ehrlichova@szu.cz
2
3 rd Faculty of Medicine, Charles University, Prague, Czech Republic;
3
Department of Cell and Molecular Biology, 3 rd Faculty of Medicine, Charles University,
Prague, Czech Republic;
4
Institute of Chemical Biology & Drug Discovery, State University of New York at Stony
Brook, Stony Brook, New York, 11794-3400, USA
As breast cancer is the most common cancer in women worldwide, infallible methods
for diagnosis and treatment are needed. Mitotic poisons taxanes are among the most
successfully used drugs in chemotherapy of breast cancer. Taxanes bind to microtubules
and cause degradation of mitotic spindle and prevent cell division. However, inherited or
acquired multidrug drug resistance (MDR) of tumor cells may occur. MDR is connected
with changes in expression levels of ABC and SLC transporters, biotransformation of
xenobiotic compounds and cell cycle modifications, too. Due to MDR, the effectiveness
of breast cancer chemotherapy is decreased or even dramatically suppressed. The aim
of this project was to explore, if the success rate of breast cancer treatment by taxanes
can be enhanced by the use of novel synthetic derivatives – second generation taxanes
and fluorinated taxanes.
Efficiency of classical, second generation and fluorinated taxanes was investigated. The
experiment was carried out with the use of human breast cancer cell lines MDA-MB-231
(taxane-sensitive) and MT-3 (taxane-resistant). First, cytotoxicity was measured by the
use of MTT kit and LC50 values were determined. HPLC analysis and liquid scintillation
were performed to show transport of paclitaxel (classical taxane) and some fluorinated
taxanes. Next, flow cytometer BD FACSVersa was used to explore changes in cell cycle
progression and to detect induction of cell death after incubation with taxanes.
The effectiveness of classical and novel taxanes in sensitive breast cancer cells was similar,
while it differed in resistant cells. Cytotoxicity test revealed that there was no observable
Analytical Cytometry VII 91