Journal
ONCOTARGET
Volume 8, Issue 15, Pages 25097-25106Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15341
Keywords
Galectin-1; multidrug resistance; P-glycoprotein; Raf-1/AP-1; breast cancer
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Galectin-1 (Gal-1), a member of the galectin family of carbohydrate binding proteins, plays a pivotal role in various cellular processes of tumorigenesis. The regulatory effect of Gal-1 on multidrug resistance (MDR) breast cancer cells is still unclear. qRT-PCR and western blot showed that Gal-1 and MDR gene 1 (MDR1) were both highly expressed in breast tumor tissues and cell lines. MTT assay and flow cytometry revealed that Gal-1 knockdown improved sensitivity to paclitaxel (PTX) and adriamycin (ADR) in MCF-7/PTX and MCF-7/ADR cells via inhibition of cell viability and promotion of cell apoptosis, while MDR1 overexpression weakened the sensitivity to PTX and ADR induced by Gal-1 knockdown. Furthermore, the negative effects of Gal-1 knockdown on sensitivity to PTX and ADR in MCF-7/PTX and MCF-7/ADR cells were revealed to be mediated via the suppression of Raf-1/AP-1 pathway. In conclusion, Gal-1 knockdown dramatically improved drug sensitivity of breast cancer by reducing P-glycoprotein (P-gp) expression via inhibiting the Raf-1/AP-1 pathway, providing a novel therapeutic target to overcome MDR in breast cancer.
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