Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effectiveness and safety. In this study, rat ventral prostatic epithelial cells were used to determine whether DHEAmodulated proliferation and prostate-specific antigen (PSA listed as KLKB1 in the MGI Database) production were mediated via the androgen receptor (AR) and its potential mechanism. We demonstrated that proliferation of prostatic epithelial cells and increase of PSA expression induced by DHEA were neutralized by Casodex or Ar siRNA, two specific AR blockers. DHEA stimulated Nfkb DNA binding activity, with this effect being blunted by Casodex or Ar siRNA. Moreover, the inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT nullified the effects of DHEA on NFKB activation. These findings suggested that DHEA stimulated normal prostatic epithelial cell proliferation, and AR is involved in DHEA-induced PSA expression in normal prostatic epithelial cells. This stimulation effect induced by DHEA is mediated by the activation of NFKB via PI3K/AKT pathway.

Propofol is a commonly used anesthetic drug with potential antitumor activity. The aim of this study was to investigate the antiproliferation and antimetastatic mechanisms of propofol in hepatocellular carcinoma (HCC). SMMC-7721 was treated with different concentrations of propofol. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell motility was assessed by the wound healing assay. Cell migration and invasion ability were analyzed by the transwell assay. Protein levels of E-cadherin, Vimentin, matrix metalloproteinase 2 (MMP-2), and MMP-9 were measured by Western blotting. Twist1 gene expression was assessed by Western blotting and quantitative reverse transcription PCR. The proliferation, motility, migration, and invasion of SMMC-7721 cells were inhibited by propofol treatment in a dose-dependent manner. Propofol treatment downregulated the protein levels of Vimentin, MMP-2, and MMP-9 while increasing that of E-cadherin. Propofol treatment inhibited the expression of the Twist1 gene in SMMC-7721 cells. The overexpression of Twist1 could partially reverse the inhibitory effects of propofol on SMMC-7721 cells. Propofol inhibited proliferation, migration, and invasion of HCC cells by downregulating the expression of Twist1, making it a potential drug for HCC treatment. K E Y W O R D S hepatocellular carcinoma (HCC), invasion, migration, propofol, Twist1