ABSTRACT
<p><b>BACKGROUND</b>Sodium 4-phenylbutanoate (NaPB) can induce cellular differentiation and cell cycle arrest. However, its potential anticancer properties in hepatocellular carcinoma and influence on normal liver cell are still unclear. We observed the effects of NaPB on growth inhibition, including differentiation and phase growth arrest in normal liver cell line L-02 and hepatocellular carcinoma cell line Bel-7402. Furthermore, we investigated its mechanism in Bel-7402. METHODS; Hepatocellular carcinoma cells Bel-7402 and normal liver cell line L-02 were treated with NaPB at different concentrations. Light microscopy was used to find morphological change in cells. Cell cycle was detected by flow cytometry. Expression of acetylating histone H4 and of histones deacetylase 4 (HDAC4) were determined by Western blot. The expression of P21WAF1/CIP1 and E-cadherin were observed through immunocytochemistry.</p><p><b>RESULTS</b>NaPB treatment led to time dependent growth inhibition in hepatocellular carcinoma cells Bel-7402. NaPB treatment caused a significant decline in the fraction of S phase cells and a significant increase in G0/G1 cells. NaPB increased the expression of P21(WAF1/CIP1) and E-cadherin in Bel-7402 and significantly decreased the level of HDAC4 in Bel-7402. NaPB significantly improved the level of acetylating histone H4. The normal liver cell line L-02 showed no distinct changes under treatment with NaPB.</p><p><b>CONCLUSIONS</b>NaPB inhibited the growth of hepatocellular carcinoma cells Bel-7402 and induced partial differentiation through enhancing the acetylating histones. In Bel-7402, the expressions of P21(WAF1/CIP1) and E-cadherin may be related to level of acetylating histones and inhibition of cellular growth. NaPB showed no significant effect on normal liver cells.</p>
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Blotting, Western , Cadherins , Carcinoma, Hepatocellular , Drug Therapy , Metabolism , Pathology , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21 , Enzyme Inhibitors , Pharmacology , Histone Deacetylase Inhibitors , Liver Neoplasms , Drug Therapy , Metabolism , Pathology , Phenylbutyrates , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic effect and mechanism of Qidan granule on blemycinA5-induced pulmonary fibrosis in rats.</p><p><b>METHODS</b>A total of 70 SD rats were randomly divided into normal group, the model group, Qidan group and hydrocortisone group and observed for 28 days and 42 days, respectively. Rat pulmonary fibrosis was induced by intrabronchial injection of blemycinA5. Treatment started from day 14 to day 42 with Qidan granule and Hydrocortisone for 14 days (day 28 group) and for 28 days (day 42 group), respectively. The lung pathological grades were observed by hematoxylin and eosin (HE) staining and expressions of transforming growth factor beta (TGF-beta(1)) protein and tumor necrosis factor alpha (TNF-alpha) protein were tested by the immunohistochemical technique.</p><p><b>RESULTS</b>(1) Lung pathobiology fibrosis were alleviated was alleviated significantly in Qidan granule group compared with those in model group and hydrocortisone group (p < 0.01). (2) In Qidan group and hydrocortisone group, the expression of TGF-beta(1) protein was 1.71 +/- 0.17 and 1, 78 +/- 0.17 in day 28 group and day 42 group, respectively. The expression of TNF-aprotein was 2.16 +/- 0.40 and 1.98 +/- 0.33 in day 28 group and day 42 group, respectively. The expression of TGF-beta(1) and TNF-alpha protein was significantly difference from those in the model group and the hydrocortisone group (p < 0.01).</p><p><b>CONCLUSIONS</b>Qidan granule ameliorate the pulmonary fibrosis by decreasing expressions of TGF-beta(1) and TNF-alpha proteins in lung tissue.</p>
Subject(s)
Animals , Male , Rats , Drugs, Chinese Herbal , Therapeutic Uses , Lung , Metabolism , Pathology , Phytotherapy , Pulmonary Fibrosis , Drug Therapy , Metabolism , Pathology , Rats, Sprague-Dawley , Transforming Growth Factor beta , Metabolism , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the anti-fibrotic effects of Qidan granule in rats.</p><p><b>METHODS</b>The rats were randomly divided into six experimental groups: normal group, model group, Qidan group, Tetrandrine group. All rats except normal group were treated with silicon dioxide (50 mg/rat) by intratracheal instillation to induce silicosis. Qidan group and Tetrandrine group were treated with Qidan granule (3125 mg/kg) or treated with Tetrandrine (22 mg/kg) respectively. All the rats were sacrificed after 5 months. Calculate Lung/body coefficient by weighting the lung wet weight and the body weight of rats. Content of Hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-beta1 was examined by using enzyme-linked immunosorbent assay (ELISA). Paraffin embedded lung sections with HE staining, VG staining and Gomori staining were observed under light microscope.</p><p><b>RESULTS</b>In Qidan group and Tetrandrine group, Lung/body coefficient and content of Hydroxyproline and expression of transforming growth factor-beta1 were lower as compared with model group (P < 0.05). Model group mainly showed III approximately IV grade silicotic nodule, which contained thick collagen and sparse reticulum fibe; Qidan group and Tetrandrine group appeared with II grade silicotic nodule, which contained tiny collagen and intensive reticulum fibe. Tetrandrine group showed injury of kidney, and others were normal.</p><p><b>CONCLUSION</b>Qidan granule extract should prevent and from inhibit the remarkably silicotic fibrosis in rats.</p>