Establishment of Paclitaxel-resistant Breast Cancer Cell Line and Nude Mice Models, and Underlying Multidrug Resistance Mechanisms in Vitro and in Vivo

Background: Breast cancer is a common malignant tumor which affects health of women and multidrugresistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted toestablish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms ofMDR.
Methods: The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalatingpaclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves weremeasured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electronmicroscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteinsrelated to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice wereinjected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxeltreatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry.
Results: Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance andprolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor(ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factorreceptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP)and glutathione-S-transferase-π (GST-π) involved in the MDR phenotype of resistant cells and tumors were alloverexpressed.
Conclusion: The underlying MDR mechanism of breast cancer may involve increased expressionof P-gp, LRP and GST-π.