open access

Vol 93, No 3 (2022)
Research paper
Published online: 2021-06-24
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Astragaloside IV inhibits cell invasion and metastasis in vulvar squamous cell carcinoma through the TGF-β1/FAK/AKT signaling pathway

Yan-Yan Zhao1, Hai-Yan Zhang1
·
Pubmed: 34263914
·
Ginekol Pol 2022;93(3):179-184.
Affiliations
  1. Department of Obstetrics and Gynecology, Baotou Central Hospital, Baotou City, Inner Mongolia, China

open access

Vol 93, No 3 (2022)
ORIGINAL PAPERS Gynecology
Published online: 2021-06-24

Abstract

Objectives: To investigate the mechanism of astragaloside IV (AS-IV) inhibiting the invasion and metastasis of vulvar squamous cell carcinoma (VSCC).

Material and methods: MTT and plate colony-formation assays were used to examine the cell proliferation of VSCC (SW962 cell line). Transwell and scratch wound-healing assays were used to analyse cell migration and invasion. Western blot was used to detect the expression of relevant proteins in terms of cell proliferation, invasion and metastasis, as well as the TGF-β1/FAK/AKT signaling pathway.

Results: The results showed that AS-IV inhibited the proliferation of SW962 cells in a concentration-dependent manner, as demonstrated by the upregulation of P53 and P21 expression and the downregulation of cyclin D1 expression. AS-IV decreased the ability of cell invasion and metastasis by the downregulation of MMP-2 and MMP-9 expression. When TGF-β1 was added to SW962 cells, the expression of the N-cadherin and Vimentin were upregulated and that of the E-cadherin was downregulated. Subsequently, fibroblast-like elongated spindle-shaped cells appeared, which suggests that TGF-β1 could induce EMT in SW962 cells. Furthermore, the expression of p-FAK, p-AKT, MMP-2 and MMP-9 were upregulated. The expression of these proteins exhibited the opposite effect after AS-IV intervention. Cell invasion and metastasis were suppressed.

Conclusions: AS-IV inhibits cell invasion and metastasis in VSCC through the TGF-β1/FAK/AKT signalling pathway.

Abstract

Objectives: To investigate the mechanism of astragaloside IV (AS-IV) inhibiting the invasion and metastasis of vulvar squamous cell carcinoma (VSCC).

Material and methods: MTT and plate colony-formation assays were used to examine the cell proliferation of VSCC (SW962 cell line). Transwell and scratch wound-healing assays were used to analyse cell migration and invasion. Western blot was used to detect the expression of relevant proteins in terms of cell proliferation, invasion and metastasis, as well as the TGF-β1/FAK/AKT signaling pathway.

Results: The results showed that AS-IV inhibited the proliferation of SW962 cells in a concentration-dependent manner, as demonstrated by the upregulation of P53 and P21 expression and the downregulation of cyclin D1 expression. AS-IV decreased the ability of cell invasion and metastasis by the downregulation of MMP-2 and MMP-9 expression. When TGF-β1 was added to SW962 cells, the expression of the N-cadherin and Vimentin were upregulated and that of the E-cadherin was downregulated. Subsequently, fibroblast-like elongated spindle-shaped cells appeared, which suggests that TGF-β1 could induce EMT in SW962 cells. Furthermore, the expression of p-FAK, p-AKT, MMP-2 and MMP-9 were upregulated. The expression of these proteins exhibited the opposite effect after AS-IV intervention. Cell invasion and metastasis were suppressed.

Conclusions: AS-IV inhibits cell invasion and metastasis in VSCC through the TGF-β1/FAK/AKT signalling pathway.

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Keywords

astragaloside IV; vulvar squamous cell carcinoma; EMT; TGF-β1; FAK/AKT pathway; metastasis

About this article
Title

Astragaloside IV inhibits cell invasion and metastasis in vulvar squamous cell carcinoma through the TGF-β1/FAK/AKT signaling pathway

Journal

Ginekologia Polska

Issue

Vol 93, No 3 (2022)

Article type

Research paper

Pages

179-184

Published online

2021-06-24

Page views

5513

Article views/downloads

909

DOI

10.5603/GP.a2021.0113

Pubmed

34263914

Bibliographic record

Ginekol Pol 2022;93(3):179-184.

Keywords

astragaloside IV
vulvar squamous cell carcinoma
EMT
TGF-β1
FAK/AKT pathway
metastasis

Authors

Yan-Yan Zhao
Hai-Yan Zhang

References (23)
  1. Ayhan A, Velipasaoglu M, Salman MC, et al. Prognostic factors for recurrence and survival in primary vulvar squamous cell cancer. Acta Obstet Gynecol Scand. 2008; 87(11): 1143–1149.
  2. Zhou J, Shan G. The prognostic role of FIGO stage in patients with vulvar cancer: a systematic review and meta-analysis. Curr Med Res Opin. 2016; 32(6): 1121–1130.
  3. Te Grootenhuis NC, Pouwer AFW, de Bock GH, et al. Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: a systematic review. Gynecol Oncol. 2018; 148(3): 622–631.
  4. Gong AGW, Duan R, Wang HY, et al. Evaluation of the pharmaceutical properties and value of astragali radix. Medicines (Basel). 2018; 5(2): 46.
  5. Li L, Hou X, Xu R, et al. Research review on the pharmacological effects of astragaloside IV. Fundam Clin Pharmacol. 2017; 31(1): 17–36.
  6. Ren S, Zhang H, Mu Y, et al. Pharmacological effects of Astragaloside IV: a literature review. J Tradit Chin Med. 2013; 33(3): 413–416.
  7. Tan B, Jia R, Wang G, et al. Astragaloside attenuates the progression of prostate cancer cells through endoplasmic reticulum stress pathways. Oncol Lett. 2018; 16(3): 3901–3906.
  8. Zheng Y, Dai Y, Liu W, et al. Astragaloside IV enhances taxol chemosensitivity of breast cancer via caveolin-1-targeting oxidant damage. J Cell Physiol. 2019; 234(4): 4277–4290.
  9. Zhu J, Wen K. Astragaloside IV inhibits TGF-β1-induced epithelial-mesenchymal transition through inhibition of the PI3K/Akt/NF-κB pathway in gastric cancer cells. Phytother Res. 2018; 32(7): 1289–1296.
  10. Xu F, Cui WQ, Wei Y, et al. Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling. J Exp Clin Cancer Res. 2018; 37(1): 207.
  11. Li B, Wang F, Liu N, et al. Astragaloside IV inhibits progression of glioma via blocking MAPK/ERK signaling pathway. Biochem Biophys Res Commun. 2017; 491(1): 98–103.
  12. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014; 15(3): 178–196.
  13. Karoń P, Olejek A, Olszak-Wasik K. TGF-β expression in vulvar cancer. Ginekol Pol. 2014; 85(11): 847–851.
  14. Zhao X, Guan JL. Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. Adv Drug Deliv Rev. 2011; 63(8): 610–615.
  15. Cicchini C, Laudadio I, Citarella F, et al. TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling. Exp Cell Res. 2008; 314(1): 143–152.
  16. Xie T, Li Y, Li SL, et al. Astragaloside IV enhances cisplatin chemosensitivity in human colorectal cancer via regulating NOTCH3. Oncol Res. 2016; 24(6): 447–453.
  17. Wang S, Mou J, Cui L, et al. Astragaloside IV inhibits cell proliferation of colorectal cancer cell lines through down-regulation of B7-H3. Biomed Pharmacother. 2018; 102: 1037–1044.
  18. Zeisberg M, Neilson E. Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 2009; 119(6): 1429–1437.
  19. Paredes J, Figueiredo J, Albergaria A, et al. Epithelial E- and P-cadherins: role and clinical significance in cancer. Biochim Biophys Acta. 2012; 1826(2): 297–311.
  20. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009; 19(2): 156–172.
  21. Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene. 2005; 24(50): 7443–7454.
  22. Gabarra-Niecko V, Schaller MD, Dunty JM. FAK regulates biological processes important for the pathogenesis of cancer. Cancer Metastasis Rev. 2003; 22(4): 359–374.
  23. Wang R, Yu Z, Chen F, et al. miR-300 regulates the epithelial-mesenchymal transition and invasion of hepatocellular carcinoma by targeting the FAK/PI3K/AKT signaling pathway. Biomed Pharmacother. 2018; 103: 1632–1642.

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