Objective: Elevated expression of Multidrug Resistance Protein 1 (MRP1) has been associated with poor prognosis among breast cancer patients. Chemotherapeutic drugs such as doxorubicin (DOX) are substrates of MRP1 that efflux the drug, conferring drug resistance. Chemoresistance is associated with the upregulation of MRP1 via Mucin 1 (MUC1). Aberrant glycosylation of MUC1 promotes tumor associated changes involved in cancer progression. Sialylation, a form of glycosylation, is regulated by the enzyme Neuraminidase 1 (Neu1) which adds 9-carbon sialic acids on glycoproteins to control cancer growth. The objective of this study was to understand the relationship between Neu1, MUC1 and MRP1 in mammary carcinoma cells as related to improving the efficacy of DOX to suppress cell growth.

Materials and Methods: MDA-MB-231 and MCF-7 cells were treated with Oseltamivir Phosphate (OP) and/or DOX to assess cell viability using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Cells transfected with Neu1 siRNA or those overexpressed with Neu1 in the presence or absence of DOX were counted using trypan blue exclusion assay. Expression levels of MUC1 and MRP1 were detected using western blotting in cells treated with oseltamivir phosphate, cells transfected with Neu1 siRNA and cells overexpressing Neu1.

Results: In this study, we demonstrated that reducing the activity of Neu1 with OP or silencing Neu1 enhanced DOX-mediated growth suppression. In addition, OP or Neu1 siRNA suppressed the protein expression of MUC1 and MRP1 while the overexpression of Neu1 reversed this effect.

Conclusions: Based on these observations, Neu1 affects the expression levels of MUC1, which in turn regulates the expression of MRP1. Consequently, this affects DOX-mediated growth suppression.