1. Salidroside inhibits migration, invasion and angiogenesis of MDA‑MB�231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2
- Author
-
Hyo Gun Lee, Youn Hee Joung, Young Mok Yang, Young Min Park, Dong Young Kang, Doh Hoon Kim, and Nipin Sp
- Subjects
STAT3 Transcription Factor ,0301 basic medicine ,Cancer Research ,MMP2 ,Cell Survival ,Angiogenesis ,Angiogenesis Inhibitors ,Triple Negative Breast Neoplasms ,Matrix metalloproteinase ,Biology ,Metastasis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,Phenols ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,STAT3 ,Salidroside ,Janus Kinase 2 ,medicine.disease ,Antineoplastic Agents, Phytogenic ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,chemistry ,Tumor progression ,030220 oncology & carcinogenesis ,STAT protein ,Cancer research ,biology.protein ,Matrix Metalloproteinase 2 ,Female ,Signal Transduction - Abstract
The major hallmarks of tumor progression are angiogenesis, migration and metastasis. Among the components of Rhodiola rosea, salidroside (p‑hydroxyphenethyl-β‑d-glucoside) is one of the most potent, and is present in all Rhodiola species. Recent data have revealed the anticancer effects of salidroside; however, the mechanism underlying its ability to inhibit tumor angiogenesis remains unknown. The present study aimed to analyze how salidroside affects major factors involved in breast cancer, and to elucidate its ability to inhibit angiogenesis and invasion. Signal transducer and activator of transcription 3 (STAT3) is a marker for tumor angiogenesis and migration, which interacts with matrix metalloproteinases (MMPs). Specifically, MMPs act as a downstream target for STAT3. Using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, the present study demonstrated that treatment of MDA‑MB 231 triple-negative breast cancer (TNBC) cells with salidroside led to inhibition of invasion and migration markers, and of STAT3 signaling. Furthermore, in vitro angiogenesis analyses in human umbilical vein endothelial cells confirmed the anti-angiogenic activity of salidroside. An electrophoretic mobility shift assay also demonstrated that salidroside may inhibit the DNA-binding activity of STAT3, preventing STAT3 from binding to a novel binding site of the MMP2 gene promoter. In conclusion, the present results demonstrated that salidroside may downregulate the STAT3 signaling pathway, and inhibit cell viability, migration and invasion through MMPs in breast cancer cells.
- Published
- 2018
- Full Text
- View/download PDF