Establishment Of Multidrug-resistant Brast Cancer Cell Line MCF-7/MDR～a And Its Prelimiary Analysis On The Biologial Property

Multidrug resistance (MDR) of tumor is one of the most important factors that lead to the failure of chemotherapy. It has valubale to establish tumor MDR cell model and research on it for the therapy favoringly on cancer. In this paper, a good cancer MDR model was established successfully. Both its drug-resistance categories and biological property were analyzed, comparing with its original cell line. We expect that it could give the reference to clinical medicaments. and give a support to analysis on mechanism of drug-resistance cell in the level of molecule.In this thesis a line of breast cancer cell named MCF-7/MDRa with multidrug-resistance was established, following the derivational cultivation with the increasing drug concentration. Its elementary biological properties including drug-resistance, cell cycle dynamics, exterior transformation, and intracellular drug accumulation and so on were analyzed. Results showed that MCF-7/MDRa was of good resistance to several chemotherapeutants for tumor,such as epirubicin and mitoxantrone. The IC50 of MCF-7/MDRa to ADM was 500 times higher than that of original cell MCF-7, and the resistance Factor still remains 200 above after MCF-7/MDRa was cultivated in blank medium. The accumulation of ADM in cells could be detected with CEC-LIF method even after 6-day cultivating in the control (the culture medium without ADM).After the drug-resistance cell was established through derivational cultivation with single drug, other 14 kinds of chemotherapy medicines were adopted to identify the drug-resistance property on MCF-7/MDRa cell, and it was ascertained to be resistant to 9 of these chemotherapy medicines intersectantly with the resistance factor from 3.06 to 127.07 times. The fission degree of drug-resistant cell was lower than that of MCF-7 cell dividing synchronously. MDR cell needed not be strict nutrition, and its multiplication time was similar to that of original cells MCF-7. The cells aggrandized notably in S-phase and decreased in G1-phase in a cell cycle. The multiplication time could be accelerated along with culturing the cells in blank medium (without ADM). The expression levels of P-gp and GSTÏ€on the cells increased significantly, while ER was not observed in this test. Furthermore,more side population cell was founded with FCM on the MCF-7/MDRa, and this cell concentration in MCF-7/MDRa was higher than that of original cells.The results indicated that the MCF-7/MDRa we established is a good cell model with MDR characteristics. This cell model is helpful to research on the MDR mechanism of cancer cells. It also suggested there may be two kinds of subclones in the drug-resistance cell line: one was intrinsic MDR cells (MCF-7/I), another was acquired MDR cells (MCF-7/MDR).