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Comparison and Characteristics of Two Paclitaxel Resistant Human Mammary Adenocarcinoma MCF-7 Cell Strains
Xiao-Ping Zhang, Yong-Hui Tao 1, Hui Hua, Jing Wu, Lian-Feng Zhang, Rong-Rong Zhang2, Jian Jin*
Laboratory of Molecular Pharmacology, School of Medicine and Pharmaceutics, Jiangnan University, Wuxi 214122, China; 1Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China; 2Wuxi No.2 People's Hospital, Wuxi 214002, China
Abstract: The foundation of cancer multidrug-resistant (MDR) study was establishment of a stable drug resistant cancer cell line. In this paper two lines of breast cancer cell named MCF-7/Taxola and MCF-7 /Taxolb with multidrug-resistance were established by gradually increasing concentration of paclitaxel (Taxol) and impacting with high dose of paclitaxel for short-time from the parent cell line MCF-7 in vitro, and their biological properties including drug-resistance, cell cycle dynamics, exterior transformation, and intracellular drug accumulation and so on, were analyzed. Results showed that the two cell lines were of good resistance to several chemotherapeutants for tumor. The IC50 of MCF-7/Taxola to paclitaxel was 525 times higher than that of nature MCF-7, and the other was 330 times. The multiplication times of the two cell lines were longer than the nature cell . The proportion of MCF-7/Taxola cells in S-phase increased while those in G1-phase decreased and MCF-7/Taxolb was like the nature cells. The expression levels of P-gp, LRP and GSTπ on the cells of MCF-7/Taxola increased, and only the GSTπ on the cells of MCF-7/Taxolb increased, and the ToPoII on the cells of the two drug resistant cell strains decreased, but the both ER and PR was not observed. The morphology of MCF-7/Taxola became larger and irregular, and the surface of nature cell was the shape of floss, but MCF-7/Taxola was the shape of bead and fluffed cotton, MCF-7/Taxolb was the the shape of fluffed cotton .The intracellular paclitaxel of MCF-7/Taxola was detected by HPLC even after 10-day culture in the medium (without paclitaxel), but not in MCF-7/Taxolb. The results indicated both the two cell lines were typical MDR cell lines which have basic characteristics of drug resistance cells. By comparing the two cell lines, it may be that the MCF-7/Taxolb was a cell subpopulation of MCF-7 /Taxola.