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

Abstract

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 ( p < 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 ( p < 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.

Influence of verapamil on the pharmacokinetics of oridonin in rats

“…2018; Yang et al. 2018; Wang and Zhu 2019). Moreover, oridonin performed synergistic antiproliferative and apoptosis-inducing effects on human myeloid leukaemia cells, when combined with valproic acid (Li and Ma 2019).…”

An Insight into the Anti-Angiogenic and Anti-Metastatic Effects of Oridonin: Current Knowledge and Future Potential

“…The anti-invasive and anti-metastatic effects of oridonin via inhibiting the mTOR pathways have been studied in ovarian cancer. The treatment with oridonin at 2.5 to 10 µM for 24 h decreased cell migration and invasion of SKOV3 ovarian cancer cells by blocking the phosphorylation of the mTOR signaling pathway [ 71 , 89 ]. The inhibition of mTOR is also accompanied by the upregulation of forkhead box P3 (FOXP3) following oridonin treatment [ 89 ].…”

“…The treatment with oridonin at 2.5 to 10 µM for 24 h decreased cell migration and invasion of SKOV3 ovarian cancer cells by blocking the phosphorylation of the mTOR signaling pathway [ 71 , 89 ]. The inhibition of mTOR is also accompanied by the upregulation of forkhead box P3 (FOXP3) following oridonin treatment [ 89 ]. FOXP3 plays a role in regulating the function of regulatory T-cell [ 90 ].…”

Oridonin Promotes Apoptosis and Restrains the Viability and Migration of Bladder Cancer by Impeding TRPM7 Expression via the ERK and AKT Signaling Pathways

“…Oridonin, a structurally analogous product of waixenicin A isolated from Rabdosia rubescens , has been documented to have a remarkable cancer-fighting and chemosensitization abilities for a broad spectrum of cancers mediated by regulating canonical oncogenic events [ 23 , 24 ]. It can impact crucial intercellular functions, such as cell proliferation, migration, invasion, apoptosis, and autophagy, and thus produces deleterious effects on tumorigenic properties in cancers [ 25 , 26 ]. However, its effects on BC have not been reported to date.…”