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.
Highlights
Breast cancer is one of the most prevalent cancers and the gradually increasing incidence of breast cancer is the leading cause of cancer death among women in the world [1]
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 MDR gene 1 (MDR1) overexpression weakened the sensitivity to PTX and ADR induced by Gal-1 knockdown
We aimed to investigate the effect of Gal-1 knockdown on cell proliferation and apoptosis of the multidrug resistance (MDR) breast cancer cell lines and the relationship between Gal-1 and Raf-1/AP-1 signaling pathway to further study the molecular mechanism of MDR, providing a novel therapeutic approach to overcome MDR in breast cancer
Summary
Breast cancer is one of the most prevalent cancers and the gradually increasing incidence of breast cancer is the leading cause of cancer death among women in the world [1]. Multidrug resistance (MDR) gradually emerges in clinical trials by using chemotherapeutic agents alone or combined with other antineoplastic agents and is becoming a major clinical obstacle and paramount factor in the failure of breast cancer chemotherapy and the human body has become insensitive to antitumor drugs due to MDR [3]. The mechanisms related to MDR are multifarious, such as the increased drug efflux, activation of DNA repair process and the deregulation of drug-induced apoptosis and the major factor of MDR pathogenesis is the high expression of MDR proteins of adenosine triphosphate (ATP)-binding cassette (ABC) transporters in cell membranes, especially multidrug efflux transporter P-glycoprotein (P-gp) [4, 5]. P-gp, a plasma membrane glycoprotein encoded by the ATP-binding cassette subfamily B member 1 (ABCB1, known as multidrug resistance gene 1 (MDR1)), is one of the main multidrug transporters and has an important impact on the absorption, distribution and elimination of chemotherapeutic drugs [6]. P-gp is regarded as the most important MDRregulatory drug target and inhibition of P-gp expression would be an effective therapeutic approach to overcome MDR and enhance the therapeutic effect
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