Functional roles of glycogene and N‐glycan in multidrug resistance of human breast cancer cells

Drug resistance is a major problem in cancer chemotherapy. Aberrant glycosylation has been known to be associated with cancer chemoresistance. Aim of this work is to investigate the alterations of glycogene and N‐glycan involved in multidrug resistance (MDR) in human breast cancer cell lines. Using real‐time polymerase chain reaction (PCR) for quantification of glycogenes, fluorescein isothiocyanate (FITC)‐lectin binding for glycan profiling, and mass spectrometry for N‐glycan composition, the expression of glycogenes, glycan profiling, and N‐glycan composition differed between drug‐resistant MCF/ADR cells and the parental MCF‐7 line. Further analysis of the N‐glycan regulation by tunicamycin (TM) application or PNGase F treatment in MCF/ADR cells showed partial inhibition of the N‐glycan biosynthesis and increased sensitivity to chemotherapeutic drugs dramatically both in vitro and in vivo. Using an RNA interference strategy, we showed that the downregulation of MGAT5 in MCF/ADR cells could enhance the chemosensitivity to antitumor drugs both in vitro and in vivo. Conversely, a stable high expression of MGAT5 in MCF‐7 cells could increase resistance to chemotherapeutic drugs both in vitro and in vivo. In conclusion, the alterations of glycogene and N‐glycan in human breast cancer cells correlate with tumor sensitivity to chemotherapeutic drug and have significant implications for the development of new treatment strategies. © 2013 IUBMB Life, 65(5):409–422, 2013.