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: Fang Wang, Pengwei Lv, Yuanting Gu, Lin Li, Xin Ge, Guangcheng Guo
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 15 Pg. 25097-25106 (Apr 11 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28212576 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Galectin 1
• Transcription Factor AP-1
• Proto-Oncogene Proteins c-raf

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects, genetics)
• Drug Resistance, Multiple (drug effects, genetics)
• Drug Resistance, Neoplasm (genetics)
• Female
• Galectin 1 (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Proto-Oncogene Proteins c-raf (metabolism)
• Signal Transduction (drug effects)
• Transcription Factor AP-1 (metabolism)