Effect of human epididymis protein 4 gene silencing on the malignant phenotype in ovarian cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human epididymis secretory protein 4 (HE4) has been proved to be a promising novel biomarker for the detection of epithelial ovarian carcinomas. Compared with CA125, HE4 assay demonstrated an improved ability to discriminate between pelvic mass with malignant and benign disease. Though it is well known that HE4 is overexpressed in ovarian cancer, however, the role of HE4 in the carcinogenesis and progression of ovarian cancer remains unkown.</p><p><b>METHODS</b>In this study, we explored the role of HE4 in the carcinogenesis and progression of ovarian cancer. We screened nine ovarian cancer cell lines for HE4 expression, and using RNA interference (RNAi), we silenced HE4 gene expression in CaoV3 and SKOV3.ip1 ovarian cancer cell lines. We assessed the effect of HE4 gene silencing on the transformed phenotype by examining the cell cycle, apoptosis, proliferation and transwell migration/invasion in vitro.</p><p><b>RESULTS</b>HE4 gene silencing induces G0/G1 arrest and blocks the progression from the G1 to S phase in CaoV3 and SKOV3.ip1 cells. HE4 knockdown also inhibited cell proliferation, migration and invasion in SKOV3.ip1 cells in vitro.</p><p><b>CONCLUSION</b>HE4 may be involved in the regulation of the cell cycle and promote ovarian cancer migration and invasion.</p>

Effects of farnesoid X receptor ligand on the metabolism of bile acids in rats with estrogen-induced intrahepatic cholestasis of pregnancy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects and mechanism of farnesoid X receptor (FXR) and its ligands on the metabolism of bile acids in rats with estrogen-induced intrahepatic cholestasis of pregnancy (ICP).</p><p><b>METHODS</b>An ICP rat model was established with estradiol benzoate (EB) injections. Then FXR ligand chenodeoxycholic acid (CDCA) was administrated (100 mg/kg daily) to ICP rats for 5 days. The serum TBA and expression of FXR and bile salt export pump (BSEP) in the rat livers were examined by immunohistochemistry and reverse transcription PCR.</p><p><b>RESULTS</b>The levels of TBA in the CDCA group rats were significantly lower than the untreated rats [(17.2+/-4.1)micromol/L vs (29.3+/-6.4)micromol/L], and the expressions of mRNA and protein of FXR were significantly higher [(0.76+/-0.09 vs 0.53+/-0.06, P<0.05 and 2.35+/-0.06 vs 1.83+/-0.05, P<0.017, respectively)], and the expressions of BSEP were also higher [(0.99+/-0.21 vs 0.76+/-0.07, P<0.017 and 1.88+/-0.03 vs 1.46+/-0.06, P<0.017, respectively)].</p><p><b>CONCLUSIONS</b>FXR plays an important role in modulating the metabolism of bile acids. CDCA can lower the levels of serum TBA by upregulating the expression of FXR and BSEP and then increasing the transport of the bile acids. These facts might present a new idea and target for the treatment of ICP.</p>

Expressions of SHP and CYP7A1 in pregnant rats with intrahepatic cholestasis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the expressions of small heterodimer partner (SHP) and target gene cholesterol-7-hydroxylase (CYP7A1) in livers of rats with intrahepatic cholestasis of pregnancy (ICP), and to study the mechanism of ICP.</p><p><b>METHODS</b>Thirty SD rats (pregnant for 15 days) were equally and randomly divided into two groups: an estradiol benzoate (EB) group and a normal saline (NS) group. Two ml blood was drawn from each rat before and on the 5th day after medicine administration to measure the levels of ALT, AST, ALP, TBA, TBIL, and DBIL. After delivery, the histopathological changes of the mother rat livers were studied. The mRNA and protein expressions of SHP and CYP7A1 in the livers were determined by RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) In the EB group, the serum levels of ALT, AST, ALP, TBA, TBil, and DBil after EB administration increased significantly (P less than 0.01), but there were no significant changes in the NS group (P more than 0.05); (2) Intrahepatic cholestasis appeared in the EB group, but not in the NS group; (3) The mRNA expressions of SHP and CYP7A1 were significantly higher in the EB group than in the NS group [(SHPmRNA: NS 0.365+/-0.0317 vs EB 0.4865+/-0.0237, P less than 0.01), (CYP7A1 mRNA: NS 0.3570+/-0.0175 vs EB 0.4802+/-0.0217, P less than 0.01)]; (4) The protein expressions of SHP and CYP7A1 were also higher in the EB group than that in the NS group [(SHP: NS 0.3762+/-0.0284 vs EB 0.5033+/-0.0274, P less than 0.01), (CYP7A1: NS 0.3570+/-0.0175 vs EB 0.4802+/-0.0217, P less than 0.01)].</p><p><b>CONCLUSION</b>Estrogen induces ICP in rats. The mRNA and protein expressions of SHP and CYP7A1 in livers of the ICP rats were increased, which causes more bile acids to be synthesized. This may be one of the mechanisms of ICP.</p>