Hepatic oval cells activated by hepatocyte apoptosis in diethylnitrosamine-induced rat liver cirrhosis

To investigate whether hepatic oval cells are activated in diethylnitrosamine [DEN]-induced rat liver cirrhosis, and to explore its mechanism. Liver cirrhosis was induced in rats [n=8] by weekly intraperitoneal injections of DEN at a dose of 50mg/kg body weight for 12 weeks followed by a 2-week wash out period. Rats [n=5] that received isovolumic vehicle served as the control group. Liver pathology was examined. Apoptotic hepatocytes were identified and quantified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling [TUNEL] assay. Oval cells were detected using immunohistochemical staining for pyruvate kinase type M2 [M2PK] and cytokeratin 19 [CK19]. The work was carried out at Renmin Hospital of Wuhan University, Wuhan, Hubei, China from February to December 2009. Liver cirrhosis developed in rats subjected to DEN administration. The TUNEL and morphology assay showed that a substantial number of hepatocytes underwent apoptosis. The apoptotic index in rats subjected to DEN administration [0.75 +/- 0.15] was much higher than normal control rats [0.10 +/- 0.05]. Both CK19 and M2PK were moderately expressed in the rat liver cirrhosis, and the expression was dispersed or forming small cords in the liver; but the expression was hardly detected in the liver tissue of normal control rats. In the DEN-induced rat liver cirrhosis, oval cells are activated and stimulated to proliferation, the mechanism of which may be related to substantial hepatocyte apoptosis in the model

Protein kinase B inhibitor enhance sensitivity of gastric cancer cell to etoposide / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the effects of etoposide on protein kinase B (PKB) activity in distinct differentiated gastric cancer cell lines and the change of sensitivity to etoposide after pretreatment by wortmannin, a PKB inhibitor. To explore the relationship between PKB activity in gastric cancer cells and their sensitivity to etoposide chemotherapy.</p><p><b>METHODS</b>Four distinct differentiated gastric cancer cell lines, including MKN-28 (well differentiated), SGC-7901 (moderate differentiated), BGC-823 (poorly differentiated) and HGC-27 (undifferentiated), were studied. The PKB activities of these cell lines were detected by nonradioactive protein-kinase assay at different time points after etoposide treatment for 0,3,6,12,24 h with or without wortmannin pretreatment. Cell viabilities were assayed by MTT and cell apoptosis was analyzed by flow cytometry.</p><p><b>RESULTS</b>Poorer differentiated gastric cancer cell lines had higher PKB activities. Etoposide treatment resulted in increase in PKB activity and apoptosis rate,and decrease in cell survival rate in a time-dependent manner in gastric cancer cell lines. Wortmannin pretreatment abolished PKB activity completely in gastric cancer cells,and decreased survival rate and increased apoptosis rate in SGC-7901, BGC-823, and HGC-27 cell lines.</p><p><b>CONCLUSIONS</b>Etoposide can induce the PKB activity in gastric cancer cell lines. Wortmannin pretreatment enhances sensitivity of median and low differentiated gastric cancer cells to etoposide chemotherapy.</p>