Oridonin inhibits metastasis of human ovarian cancer cells by suppressing the mTOR pathway.

INTRODUCTION

Oridonin, which is isolated from the Chinese herb Rabdosia rubescens, has been reported to exhibit an anti-tumorous effect on different cancers. In this study, we investigated the molecular mechanism by which oridonin suppresses human ovarian cancer.

MATERIAL AND METHODS

The inhibition of oridonin on cell proliferation was assessed by CCK8 assay. Cell cycle and apoptosis were analyzed by flow cytometry, staining with propidium iodide (PI) or annexin-V/PI respectively. The metastasis rate was evaluated using a transwell migration assay. The expression of metastasis-associated genes and mTOR pathway related genes were detected by western blot.

RESULTS

We demonstrated that oridonin suppressed the proliferation and blocked the cell cycle in G1/S phage and induced apoptosis in SKOV3 and A2780 cells ( < 0.01). We further found that the mTOR signaling pathway was suppressed by the treatment with oridonin, and the activation of the mTOR pathway attenuated the anti-tumorous effect of oridonin in human ovarian cancer cells, suggesting that the mTOR pathway was involved in the anti-tumorous process of oridonin. Additionally, the activation of the mTOR pathway by an exogenous activator reduced the expression level of FOXP3 ( < 0.01), thus providing evidence that FOXP3 is a factor that is necessary for the anti-tumorous effect of oridonin, and is negatively regulated by the mTOR pathway.

CONCLUSIONS

These results suggested that oridonin suppressed the mTOR signaling pathway, up-regulated the FOXP3 level, and inhibited metastasis of human ovarian cancer cells.