Silibinin downregulates MMP2 expression via Jak2/STAT3 pathway and inhibits the migration and invasive potential in MDA-MB-231 cells

Byun, Hyo Joo; Darvin, Pramod; Kang, Dong Young; Sp, Nipin; Joung, Youn Hee; Park, Jong Hwan; Kim, Jong Hun; Yang, Young Mok

doi:10.3892/or.2017.5588

Cited by 54 publications

(36 citation statements)

References 37 publications

(41 reference statements)

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“…In addition, the JAK2‐STAT3 pathway is activated and implicated in colon cancer, breast cancer, hepatocellular carcinoma, osteosarcoma melanoma, and so on. It has also been demonstrated that MMP2 and MMP9 are linked to the STAT3 pathway . The present study also observed phosphorylation activation of the JAK2‐STAT3 signaling pathway in WRO cells and salidroside decreased expression of pJAK2 (Y1007+Y1008) and pSTAT3 (Tyr705).…”

Section: Discussionsupporting

confidence: 79%

“…It has also been demonstrated that MMP2 and MMP9 are linked to the STAT3 pathway. 39,40 The present study also observed phosphorylation activation of the JAK2-STAT3 signaling pathway in WRO cells and salidroside decreased expression of pJAK2 (Y1007+Y1008) and pSTAT3 (Tyr705). The above results suggested that salidroside may exert anti-tumor effects by inhibition of the JAK2-STAT3 pathway.…”

Section: Discussionsupporting

confidence: 76%

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Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells

et al. 2019

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Background No effective treatment is currently available for poorly differentiated thyroid cancer which is resistant to radioiodine, especially with migration and invasion. A great number of researches have revealed the anticancer effects of salidroside, but none have studied the effects of salidroside on thyroid cancer. This study aimed to investigate the effect of salidroside on migration and invasion of poorly differentiated thyroid cancer cells. Methods The effects of salidroside on migration, invasion and apoptosis of poorly differentiated thyroid cancer WRO cells and normal thyroid follicular epithelial Nthy‐ori 3‐1 cells were measured by wound‐healing assay, transwell migration/invasion assay and flow cytometry, respectively. The expression levels of MMP2 and MMP9 at RNA and protein levels in WRO cells were detected by qRT‐PCR and western blot. The phosphorylation levels of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and the apoptosis‐related protein levels of Bax, cleaved caspase 3 and Bcl‐2 were assessed by western blot. Results Salidroside significantly suppressed migration/invasion and induced apoptosis in poorly differentiated thyroid cancer WRO cells. We further illustrated that salidroside significantly inhibited expressions of MMP2 and MMP9 at mRNA and protein levels and the phosphorylation activation of JAK2/STAT3 in WRO cells. In addition, salidroside increased expressions of pro‐apoptotic factors (Bax and cleaved caspase 3) and decreased expression of anti‐apoptotic factor (Bcl‐2) significantly in WRO cells. Conclusion The present study demonstrates that salidroside inhibits migration and invasion of WRO cells (a kind of poorly differentiated cancer cell line) significantly, which might be via suppressing JAK2‐STAT3 signaling pathway.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 76%

Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells

et al. 2019

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“…A recent study reported that STAT3 activation regulates MMP2 expression (20). MMP2 transcription requires translocation of p-STAT3 to the nucleus, where it binds to the MMP2 gene promoter.…”

Section: Salidroside Inhibits Nuclear Translocation and Dna-binding Amentioning

confidence: 99%

“…3C). In our previous study, the MMP2 gene promoter was analyzed, in order to detect a γ-interferon activation site (GAS) element (20), which is the DNA-binding sequence for the STAT family of transcription factors. Upon locating this element, an EMSA was conducted to analyze the DNA-binding activity of STAT3 to the GAS element.…”

Section: Salidroside Inhibits Nuclear Translocation and Dna-binding Amentioning

confidence: 99%

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

Kang

Kim

et al. 2018

Int J Oncol

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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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“…Moreover, MMP2 and MMP9 expression levels in VSMcs have been reported to be associated with aS (37-39) by regulating the proliferation and migration of VSMcs (40,41), indicating a pathogenic role for MMP2 and MMP9 in regulating the progression of aS. Furthermore, previous studies have demonstrated that the downregulation of MMP2 and MMP9 inhibit cell migration (42)(43)(44). consistent with previous studies, in the present study, the suppression of MMP2 and MMP9 by transfection with mir-142-5p inhibitor contributed to the decreased migration of HASMCs.…”

Section: Discussionmentioning

confidence: 97%

Downregulation of miR‑142‑5p inhibits human aortic smooth muscle cell proliferation and migration by targeting MKL2

Shang

Dai

et al. 2020

Mol Med Rep

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The increased proliferation and migration of vascular smooth muscle cells (VSMcs) are critical in the progression of atherosclerosis (aS). Platelet-derived growth factor type BB (PdGF-BB) may induce VSMc proliferation and migration. mir-142-5p plays a critical role in various biological processes, including tumorigenesis, angiogenesis and inflammation. However, whether miR-142-5p is involved in regulating the pathological process of arteriosclerosis remains to be elucidated. Therefore, in this study, the role of mir-142-5p in PdGF-BB-induced human aortic smooth muscle cell (HSAMC) proliferation and migration was investigated. The results revealed that the expression level of mir-142-5p was enhanced in the serum of patients with aS, while that of its target gene, myocardin-like protein 2 (MKl2) was decreased, compared with that in healthy volunteers. Moreover, there was a negative correlation between mir-142-5p and MKl2 expression in the serum of patients with aS. Furthermore, the downregulation of miR-142-5p inhibited PDGF-BB-induced HASMC proliferation and migration; however, the inhibition of HASMC proliferation and migration was reversed by co-transfection with small interfering rna (sirna) against MKl2 (sirna-MKl2). in addition, transfection with mir-142-5p inhibitor significantly increased the expression levels of MKl2, and decreased those of matrix metalloproteinase (MMP)2 and 9, and these effects were reversed by transfection with sirna-MKl2. Finally, MKl2 was proven to be a target of miR-142-5p. On the whole, the findings of the present study demonstrate that the downregulation of mir-142-5p inhibits human aortic smooth muscle cell (HSAMC) proliferation and migration possibly by targeting MKL2. Hence, miR-142-5p may prove to be a novel therapeutic target in the treatment of aS.

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Silibinin downregulates MMP2 expression via Jak2/STAT3 pathway and inhibits the migration and invasive potential in MDA-MB-231 cells

Cited by 54 publications

References 37 publications

Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells

Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells

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

Downregulation of miR‑142‑5p inhibits human aortic smooth muscle cell proliferation and migration by targeting MKL2

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