title: Galectin-1 knockdown improves drug sensitivity of breast cancer by reducing P-glycoprotein expression through inhibiting the Raf-1/AP-1 signaling pathway.
abstract: 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.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, 450000, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, 450000, China.
authors.forename: Pengwei
authors.initials: P
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, 450000, China.
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, 450000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, 450000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, 450000, China.
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Guo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D037483:Galectin 1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D037483:Galectin 1; D018808:Transcription Factor AP-1; D019908:Proto-Oncogene Proteins c-raf
keywords: Galectin-1; P-glycoprotein; Raf-1/AP-1; breast cancer; multidrug resistance