Study On The Relationship Between Inhibiting The Proliferation Effect Of Oridonin And PTEN In HCT116 Cells

Oridonin(ORI) has been well reported as an anti-proliferation and apoptosis-inducing natural product in various cancer cell lines. However,the exact molecular mechanism underlying these effects remains unclear. In this investigation, we tested the anti-proliferation effect of ORI in HCT116 cells, and dissected the possible molecular mechanism mediating this effect.We found that ORI inhibited proliferation, induced apoptosis and made the HCT116 cells arrest cell cycle; ORI also inhibited the tumor growth in a xenograft colon cancer model. With PCR, Western blot, and immunohistochemical staining assay, we demonstrated that ORI has no substantial effect on the mRNA expression of PTEN, but increased the total protein level of PTEN and reduced the phosphorylation of PTEN markedly.Exogenous expression of PTEN potentiated the anticancer effect of ORI,while knockdown of PTEN attenuated this effect of ORI. ORI also promtied the activation of MAPKs p38 with concentration- dependent manner, and inhibition of p38 reduced the antiproliferation effect ORI inHCT116 cells. Meanwhile, inhibition of p38 increased the phosphorylation of p38, and reversed the ORI-induced decrease of PTEN phosphorylation.Our findings suggested that ORI may be a potential anticancer drug for colon cancer, which is associtated with up-regulating the level of PTEN through reducing the phosphorylation mediated by the ORI-induced activation of MAPKs p38. Therefore, ORI can be used as an effective adjuvant reagent for the clinical management of human colon cancer.