Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells

摘要: Chemotherapy resistance is the major reason for failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves upregulation multidrug (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out tumor cells. As a common symptom in stage III/IV patients, ascites associated with progression. However, whether drives cells awaits elucidation. Here, we demonstrate when cultured derived from cancer-bearing mice, murine cell line became less sensitive to paclitaxel, first chemotherapeutic agent patients. Moreover, incubation vitro efflux function these Functional studies show ascites-driven suppressible by specific inhibitors either two ABC transporters [Multidrug Related Protein (MRP1); Breast Cancer (BCRP)]. To relevance our findings studied relative human obtained patient or primary tumor. Immortalized lines developed increased susceptibility (MRP1, BCRP) compared cancer, suggesting an association between and cancer. Efflux ascites-derived expression tumor-derived Collectively, identify novel activity promoting resistance.