MDR1 (multidrug resistence 1) can regulate GCS (glucosylceramide synthase) in breast cancer cells

Abstract

Besides MDR1/P-glycoprotein (MDR1/P-gp), glucosylceramide synthase (GCS), an enzyme, which transfers UDP-glucose to ceramide to form glucosylceramide was also related with multidrug resistance (MDR) in breast cancer. Although many research showed that GCS could affect mdr1 in cancer cells, nobody knows that whether mdr1 can affect GCS in breast cancer. Our study aims to verify that. A plasmid with multidrug resistence 1(mdr1) cDNA was transfected into the sensitive breast cancer cell line MCF-7, while an RNA interference (RNAi) vector targeted mdr1 was transfected into the MDR cell line MCF-7/ADM. Then RT-PCR, Western blot, MTT, and flow cytometry were used to assess the expression and function of mdr1 and GCS. The data displayed that up-regulation of mdr1 could increase the expression of GCS, while the RNAi-expression plasmids could decrease that. Meantime, the changes of ceramide are opposed to that of GCS and are the same to the alteration of apoptosis rate. Our results demonstrate that MDR1 could increase cellular apoptosis by regulating the expression of GCS in breast cancer cells.