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Establishment of Multidrug-resistant Brast Cancer Cell Line MCF-7/MDR～a and Its Prelimiary Analysis on the Biologial Property

Author: YanZuo
Tutor: JinJian
School: Jiangnan University
Course: Microbial and Biochemical Pharmacy
Keywords: Breast Cancer Cell lines MCF-7/MDRa Adriamycin Multidrug resistance
CLC: R737.9
Type: Master's thesis
Year: 2006
Downloads: 197
Quote: 0
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Abstract


Multidrug resistance is one of the main reasons for failure of clinical cancer chemotherapy, multidrug resistant model and its nature, has a very important significance to the smooth progress of the cancer treatment. In this thesis, through the establishment of multidrug resistant model, determination of its complete resistance spectrum and compare its biological characteristics and parental cells, on the one hand to provide a reference for the clinical use of drugs, but also from the molecular level analysis mechanisms to provide a basis for drug-resistant cells. The subject first low concentration plus sustained induction of established human breast cancer MCF-7 cells resistant to doxorubicin model named MCF-7/MDRa. Its main biological characteristics, including drug resistance, kinetic cycle distribution, changes in the phenotype, intracellular drug accumulation in this experiment were more comprehensive and in-depth research. The results show that MCF-7/MDRa has good resistance to many types of cancer chemotherapy drugs; MCF-7/MDRa cells compared with parental cells ADM median lethal concentration (IC50) 500 times, drug withdrawal after 150 days of culture resistant multiple still maintained at more than 200 times. CEC-LIF method, ADM accumulation culture 6 day cells can be detected in the stable growth of drug withdrawal. Resistant cells were induced with a single drug, the choice of 14 different chemotherapy drugs MCF-7/MDRa cell identification of multidrug resistance. MCF-7/MDRa cells 3.06 to 127.07 times the cross-resistance of 9 drugs, MCF-7/MDRa cell multidrug resistance. Resistant cell differentiation degree lower than the simultaneous passage of MCF-7 / S cells, reduce the nutritional requirements of cell doubling time and parental cells close to a significant increase in S phase cells, decrease in G1 phase cells; With the withdrawal time extension, cell the proliferation speed. Immunohistochemical method for the determination of drug resistance related protein expression changes before and after found the resistant cell P-gp and GSTπ the expression levels than parental cells significantly increased loss of ER positive expression; discovered by flow cytometry of MCF-7 / MDRa in the content of side population cells than the parental cells. Basic biological characteristics established in this experiment MCF-7/MDRa model with multi-drug resistant cells, can be used for the study of multidrug resistance mechanisms, the results suggest that there may be two subclones resistant cells, The ie: congenital multidrug resistant cells MCF-7 / I and obtained multi-drug resistant cells MCF-7/MDR.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Breast tumor
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