Proteomic analysis of proteins associated with the paclitaxel-induced drug-resistant human breast cancer cells

OBJECTIVE: To investigate multidrug resistance (MDR) in the paclitaxel-induced drug-resistant breast cancer MCF-7 cells (MCF-7/Tax) using proteomic analysis. METHODS: MCF-7/Tax cell line was established by escalating the concentrations of paclitaxel to drug-sensitive MCF-7 cells (MCF-7/S). The biological characteristics of MCF-7/Tax cells were analyzed using MTT test and flow cytometry. The global protein profiles of MCF-7/Tax and MCF-7/S were compared using two-dimensional gel electrophoresis (2-DF) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). We confirmed the protein and mRNA levels of five differential patterns of expression by Western blot and Real-time PCR, respectively. RESULTS: The resistance factor of MCF-7/Tax was 115. Significant differential expressions of 17 proteins between MCF-7/Tax and MCF-7/S were identified with 11 proteins upregulated and six proteins downregulated in MCF-7/Tax cells. With western blot and real-time PCR, we confirmed that heterogeneous nuclear ribonucleoprotein (hnRNP C1/C2), SET nuclear oncogene (SET), aspartate aminotransferase (AAT), transgelin-2 were upregulated, and nucleoside-diphosphate kinase A (NDKA) was downregulated in MCF-7/Tax cells. CONCLUSION: The identification of differential proteins, particularly transgelin-2 provides new insights into the mechanism of MDR to paclitaxel and novel biological targets for breast cancer treatment.