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. 2017 May;25(4):638-643.
doi: 10.1016/j.jsps.2017.04.037. Epub 2017 May 10.

Oridonin inhibits breast cancer growth and metastasis through blocking the Notch signaling

Affiliations

Oridonin inhibits breast cancer growth and metastasis through blocking the Notch signaling

Shixin Xia et al. Saudi Pharm J. 2017 May.

Abstract

Background: Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to inhibit growth and metastasis of human breast cancer cells.

Methods: The effect of oridonin on proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in human breast cancer cells. The inhibitive effect of oridonin in vivo was determined by using xenografted nude mice. In addition, the expression of Notch receptors (Notch 1-4) was detected by western blot.

Results: Oridonin inhibited human breast cancer cells in vitro and in vivo. In addition, oridonin significantly induced human breast cancer cells apoptosis. Furthermore, the oridonin treatment not only inhibited cancer cell migration and invasion, but more significantly, decreased the expression of Notch 1-4 protein.

Conclusion: Our results suggest that the inhibitive effect of oridonin is likely to be driven by the inhibition of Notch signaling pathway and the resulting increased apoptosis.

Keywords: Breast cancer; Cell apoptosis; Notch signaling pathway; Oridonin.

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Figures

Fig. 1
Fig. 1
Chemical structures of oridonin.
Fig. 2
Fig. 2
Oridonin display potent antiproliferative and proapoptotic effects on human breast cancer cells. A: MTT assays showing inhibition of viable cells after a 24-h treatment with different concentrations of oridonin. B and C: cells were treated with oridonin (0, 0.1, 1, 5, and 10 mmol/L) for 24 h, then the percentages of cells undergoing apoptosis were determined by FITC–Annexin V/PI staining and flow cytometry and shown in B, and the percentage of Rh123-negative cells are shown in C. *P < 0.05, **P < 0.01 compared with the 0 mmol/L group.
Fig. 3
Fig. 3
Oridonin inhibits the growth of xenografted 4T1 cells in nude mice. (A) Tumor growth after treatment with oridonin. The treatment for each group was administered once daily for 21 days, with a 1-day interval every 6 days. (B) Tumor weight at 28 days after treatment. Data are expressed as means ± SD (n = 8). *P < 0.05, **P < 0.01, compared with the 0 mmol/L group.
Fig. 4
Fig. 4
Oridonin inhibits human breast cancer cell migration and invasion in vitro. A. Transwell migration assay of T41 cells treated with oridonin. B. Transwell invasion assay of T41 cells treated with oridonin. *P < 0.05, **P < 0.01, compared with the 0 mmol/L group.
Fig. 5
Fig. 5
Notch signaling pathway is the oridonin _target in ovarian cancer. A. Notch 1–4 expression in 4T1 cells was inhibited by oridonin. B. Notch 1 attenuated the suppressive effect of oridonin on ovarian cancer cell proliferation. C. The Notch 1 transfected 4T1 cell transwell migration assay. D. The Notch 1 transfected 4T1 cell transwell invasion assay. E. The qRT-PCR was conducted to detect Notch 1 expression. **P < 0.01.

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