Salidroside inhibits migration, invasion and angiogenesis of MDA‑MB 231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2

Kang,Dong Young; Sp,Nipin; Kim,Doh Hoon; Joung,Youn Hee; Lee,Hyo Gun; Park,Young Min; Yang,Young Mok

doi:10.3892/ijo.2018.4430

Salidroside inhibits migration, invasion and angiogenesis of MDA‑MB 231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2

Authors:
- Dong Young Kang
- Nipin Sp
- Doh Hoon Kim
- Youn Hee Joung
- Hyo Gun Lee
- Young Min Park
- Young Mok Yang
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Affiliations: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju, Chungcheongbuk 27478, Republic of Korea, Department of Animal Science, College of Natural Resources and Life Sciences, Pusan National University, Miryang, Gyeongsangnam 50463, Republic of Korea, Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju, Chungcheongbuk 27478, Republic of Korea
Published online on: June 5, 2018 https://doi.org/10.3892/ijo.2018.4430
Pages: 877-885

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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.

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