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Article Open Access

Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo

  • Authors:
    • Chunyu Li
    • Qi Wang
    • Shen Shen
    • Xiaolu Wei
    • Guoxia Li
  • View Affiliations / Copyright

    Affiliations: Department of Integrated Chinese Traditional and Western Medicine, International Medical School, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2289-2298
    |
    Published online on: June 11, 2018
       https://doi.org/10.3892/ol.2018.8943
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Abstract

Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from Rabdosia rubescens, was identified to be the most potent anti‑tumor ingredient. However, the molecular mechanisms responsible for its anti‑metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA‑MB‑231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose‑dependent manner. The expression levels of epithelial‑mesenchymal transition (EMT)‑associated marker and the hypoxia inducible factor 1α (HIF‑1α)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively in vitro. The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E‑cadherin, and decreased expression of N‑cadherin, Vimentin and Snail. In addition, oridonin exerted its anti‑angiogenesis activity through significantly decreasing HIF‑1α, VEGF‑A and VEGF receptor‑2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro‑vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF‑1α/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti‑metastatic agent in breast cancer treatment.
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View References

1 

Ramasamy T, Sundaramoorthy P, Ruttala HB, Choi Y, Shin WH, Jeong JH, Ku SK, Choi HG, Kim HM, Yong CS and Kim JO: Polyunsaturated fatty acid-based targeted nanotherapeutics to enhance the therapeutic efficacy of docetaxel. Drug Deliv. 24:1262–1272. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Neelakantan D, Zhou H, Oliphant MUJ, Zhang X, Simon LM, Henke DM, Shaw CA, Wu MF, Hilsenbeck SG, White LD, et al: EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun. 8:157732017. View Article : Google Scholar : PubMed/NCBI

3 

Zhou T, Zhang A, Kuang G, Gong X, Jiang R, Lin D, Li J and Li H, Zhang X, Wan J and Li H: Baicalin inhibits the metastasis of highly aggressive breast cancer cells by reversing epithelial-to-mesenchymal transition by targeting β-catenin signaling. Oncol Rep. 38:3599–3607. 2017.PubMed/NCBI

4 

Sohn EJ, Jung DB, Lee H, Han I, Lee J, Lee H and Kim SH: CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells. Cancer Lett. 412:88–98. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Zhang Y, Liu J, Lin J, Zhou L, Song Y, Wei B, Luo X, Chen Z, Chen Y, Xiong J, et al: The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer. Oncotarget. 7:9859–9875. 2016.PubMed/NCBI

6 

Yehia L, Boulos F, Jabbour M, Mahfoud Z, Fakhruddin N and El-Sabban M: Expression of HIF-1α and markers of angiogenesis are not significantly different in triple negative breast cancer compared to other breast cancer molecular subtypes: Implications for future therapy. PLoS One. 10:e01293562015. View Article : Google Scholar : PubMed/NCBI

7 

Pakravan K, Babashah S, Sadeghizadeh M, Mowla SJ, Mossahebi-Mohammadi M, Ataei F, Dana N and Javan M: MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. Cell Oncol. 40:457–470. 2017. View Article : Google Scholar

8 

Shao C, Zhang J, Fu J and Ling F: The potential role of Brachyury in inducing epithelial-to-mesenchymal transition (EMT) and HIF-1α expression in breast cancer cells. Biochem Biophys Res Commun. 467:1083–1089. 2015. View Article : Google Scholar : PubMed/NCBI

9 

He Z, Xiao X, Li S, Guo Y, Huang Q, Shi X, Wang X and Liu Y: Oridonin induces apoptosis and reverses drug resistance in cisplatin resistant human gastric cancer cells. Oncol Lett. 14:2499–2504. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Dong Y, Zhang T, Li J, Deng H, Song Y, Zhai D, Peng Y, Lu X, Liu M, Zhao Y and Yi Z: Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the Notch signaling. PLoS One. 9:e1138302014. View Article : Google Scholar : PubMed/NCBI

11 

Liu H, Qian C and Shen Z: Anti-tumor activity of oridonin on SNU-5 subcutaneous xenograft model via regulation of c-Met pathway. Tumour Biol. 35:9139–9146. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Cui XY, Tinholt M, Stavik B, Dahm AE, Kanse S, Jin Y, Seidl S, Sahlberg KK, Iversen N, Skretting G and Sandset PM: Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer. J Thromb Haemost. 14:387–396. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Lopes FC, Ferreira R, Albuquerque DM, Silveira AA, Costa R, Soares R, Costa FF and Conran N: In vitro and in vivo anti-angiogenic effects of hydroxyurea. Microvasc Res. 94:106–113. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Chen H, Zhang L, Long X, Li P, Chen S, Kuang W and Guo J: Sargassum fusiforme polysaccharides inhibit VEGF-A-related angiogenesis and proliferation of lung cancer in vitro and in vivo. Biomed Pharmacother. 85:22–27. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Kang Z, Jiang W, Luan H, Zhao F and Zhang S: Cornin induces angiogenesis through PI3K-Akt-eNOS-VEGF signaling pathway. Food Chem Toxicol. 58:340–346. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitiative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

17 

An J, Wang L, Zhao Y, Hao Q, Zhang Y, Zhang J, Yang C, Liu L, Wang W, Fang D, et al: Effects of FSTL1 on cell proliferation in breast cancer cell line MDA-MB-231 and its brain metastatic variant MDA-MB-231-BR. Oncol Rep. 38:3001–3010. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Hu H, Huang G, Wang H, Li X, Wang X, Feng Y, Tan B and Chen T: Inhibition effect of triptolide on human epithelial ovarian cancer via adjusting cellular immunity and angiogenesis. Oncol Rep. 39:1191–1196. 2017.PubMed/NCBI

19 

Ko P, Kim D, You E, Jung J, Oh S, Kim J, Lee KH and Rhee S: Extracellular matrix rigidity-dependent sphingosine-1-phosphate secretion regulates metastatic cancer cell invasion and adhesion. Sci Rep. 6:215642016. View Article : Google Scholar : PubMed/NCBI

20 

Xia S, Zhang X, Li C and Guan H: Oridonin inhibits breast cancer growth and metastasis through blocking the Notch signaling. Saudi Pharm J. 25:638–643. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Ikezoe T, Chen SS, Tong XJ, Heber D, Taguchi H and Koeffler HP: Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells. Int J Oncol. 23:1187–1193. 2003.PubMed/NCBI

22 

Li CY, Wang Q, Shen S, Wei XL and Li GX: Oridonin inhibits migration, invasion, adhesion and TGF-β1-induced epithelial-mesenchymal transition of melanoma cells by inhibiting the activity of PI3K/Akt/GSK-3β signaling pathway. Oncol Lett. 15:1362–1372. 2018.PubMed/NCBI

23 

Li Y and Galileo DS: Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion. Cancer Cell Int. 10:342010. View Article : Google Scholar : PubMed/NCBI

24 

Matysiak M, Kapka-Skrzypczak L, Jodłowska-Jędrych B and Kruszewski M: EMT promoting transcription factors as prognostic markers in human breast cancer. Arch Gynecol Obstet. 295:817–825. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Yan LX, Liu YH, Xiang JW, Wu QN, Xu LB, Luo XL, Zhu XL, Liu C, Xu FP, Luo DL, et al: PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer. Int J Oncol. 48:471–484. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Huang T, Chen Z and Fang L: Curcumin inhibits LPS-induced EMT through downregulation of NF-κB-Snail signaling in breast cancer cells. Oncol Rep. 29:117–124. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Yu JM, Sun W, Hua F, Xie J, Lin H, Zhou DD and Hu ZW: BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells. Cancer Lett. 365:190–200. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Kim DH, Sung B, Kim JA, Kang YJ, Hwang SY, Hwang NL, Suh H, Choi YH, Im E, Chung HY and Kim ND: HS-1793, a resveratrol analogue, downregulates the expression of hypoxia-induced HIF-1 and VEGF and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model. Int J Oncol. 51:715–723. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Zhang E, Shi H, Yang L, Wu X and Wang Z: Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth. Oncol Rep. 38:359–367. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Liang S, Chen Z, Jiang G, Zhou Y, Liu Q, Su Q, Wei W, Du J and Wang H: Activation of GPER suppresses migration and angiogenesis of triple negative breast cancer via inhibition of NF-κB/IL-6 signals. Cancer Lett. 386:12–23. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Cook MT, Liang Y, Besch-Williford C, Goyette S, Mafuvadze B and Hyder SM: Luteolin inhibits progestin-dependent angiogenesis, stem cell-like characteristics, and growth of human breast cancer xenografts. Springerplus. 4:4442015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li C, Wang Q, Shen S, Wei X and Li G: Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo. Oncol Lett 16: 2289-2298, 2018.
APA
Li, C., Wang, Q., Shen, S., Wei, X., & Li, G. (2018). Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo. Oncology Letters, 16, 2289-2298. https://doi.org/10.3892/ol.2018.8943
MLA
Li, C., Wang, Q., Shen, S., Wei, X., Li, G."Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo". Oncology Letters 16.2 (2018): 2289-2298.
Chicago
Li, C., Wang, Q., Shen, S., Wei, X., Li, G."Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo". Oncology Letters 16, no. 2 (2018): 2289-2298. https://doi.org/10.3892/ol.2018.8943
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Wang Q, Shen S, Wei X and Li G: Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo. Oncol Lett 16: 2289-2298, 2018.
APA
Li, C., Wang, Q., Shen, S., Wei, X., & Li, G. (2018). Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo. Oncology Letters, 16, 2289-2298. https://doi.org/10.3892/ol.2018.8943
MLA
Li, C., Wang, Q., Shen, S., Wei, X., Li, G."Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo". Oncology Letters 16.2 (2018): 2289-2298.
Chicago
Li, C., Wang, Q., Shen, S., Wei, X., Li, G."Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo". Oncology Letters 16, no. 2 (2018): 2289-2298. https://doi.org/10.3892/ol.2018.8943
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