ABSTRACT
Objective Bile acids (BA) facilitate cholesterol hepatic fibrosis. Although hepatic stellate cell (HSC) is one of the moot important cells during liver fibrogenesis, the effect of bile acids on HSC is rarely mentioned. Therefore,bile acids facilitate liver fibrosis through regulating activated HSC should be tested. Methods The amount of BrdU incor-poration was determined to assess the proliferation of HSC treated by bile acid. Wound-healing assay was used to determine the cellular motility. Meanwhile, the phoophorylation of p38 and JNK in HSC was detected by Western blotting. Results50 μmol/L GCDCA enhanced the HSC proliferation significantly (152.0% ± 7.1%, P < 0.05); 50 μmol/L GCDCA also induced phoophorylation of p38 and JNK (450.0% ± 12.2% of control in p38 (P < 0.01 ), 210.0% ± 15.2 % of control in JNK (P<0.05)). 50 μmol/L GCDCA aided wound healing (remaining wound area is 75.4% + 5.8% of original area, P<0.05), but this effect was inhibited by JNK (SP600125) or p38 (SB294002) inhibitor, respectively. Conclusions Bile acids enhance HSC proliferation and facilitate cellular motility through inducing phosphorylation of p38 and JNK, indicating bile acid aid liver fibrosis through regulation of p38 and JNK signaling.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory effect of dehydroepaimdrosterone (DHEA) on the growth of transplanted Morris hepatomas (7288CTC) in vivo in rats.</p><p><b>METHODS</b>21 Buffalo rats were randomly devided into 4 groups, including one blank control group (n = 5), one group for tumor-bearing control (n = 6), and 2 experimental groups with DHEA (n = 6) or DHEA-s (n = 4). DHEA or DHEA-s was fed to the rats for 4 weeks immediately after Morris hepatomas (7288CTC) was implanted in both flanks. Phenotypes of the spleen lymphocytes were examined by flow cytometry, Akt and PTEN expression in tumor cells was detected by Western blot and immunohistochemistry.</p><p><b>RESULTS</b>Tumor weights of DHEA treated group were less than those of the control (P less than 0.05), the inhibitory rate was 43%. The results of Western blot and immunohistochemistry showed that in DHEA tumor group,the expression of phosphorilated Akt protein was decreased, the expression of PTEN was enhanced, the percentage of CD3 positive cells and the ratio of CD4/CD8 were increased (P less than 0.05).</p><p><b>CONCLUSION</b>DHEA can inhibit tumor growth, possibly via the inhibition of the Akt signaling pathway as well as modulating the immune function.</p>
Subject(s)
Animals , Rats , Antineoplastic Agents , Pharmacology , CD4-Positive T-Lymphocytes , Allergy and Immunology , CD8-Positive T-Lymphocytes , Allergy and Immunology , Dehydroepiandrosterone , Pharmacology , Dehydroepiandrosterone Sulfate , Pharmacology , Flow Cytometry , Immunohistochemistry , Liver Neoplasms, Experimental , Allergy and Immunology , Metabolism , Pathology , Neoplasm Transplantation , PTEN Phosphohydrolase , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Random Allocation , Rats, Inbred BUF , Signal TransductionABSTRACT
Objective To study the inhibitory effects of dehydroepiandrosterone (DHEA) and its metabolites-dehydroepiandrosterone sulfate (DHEAs) on the proliferation of HepG2 and HT-29 and their mechanism.Methods HepG2 and HT-29 were incubated by DHEA or DHEAs with different concentrations (1,10,50,100 and 200 ?mol?L-1) for 8,24,48,72 h and routine culture was used as control.The inhibitory rate was detected by using MTT chromometry and BrdU assay respectively.The activities of 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR),glucose -6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) were examined simultaneously.Results ①MTT chromometry:DHEA with different concentrations obviously inhibited the growth of HepG2 and HT-29 cells compared with control group(P0.05).②BrdU assay:the growth of cells were significantly inhibited by DHEA with concentrations of 50,100 and 200 ?mol?L-1,especially to HepG2 cells(P0.05).Conclusion DHEA has strong anti-proliferative effects on both HepG2 and HT-29 cell lines and inhibitory effects on the activities of G6PD or HMGR,however,DHEAs has no obvious effect.