ABSTRACT
The expression levels of hypoxia-inducible factor 1alpha (HIF-1α) and HIF-2α in pancreatic cancer (PC) and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1α and HIF-2α mRNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1α and HIF-2α protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF-1α or HIF-2α and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1α and HIF-2α mRNA was up-regulated in most cancer tissues (P<0.05). HIF-1α staining was weakly positive in most cancer tissues and strongly positive in adjacent pancreas tissues (P<0.05). Clinicopathologic analysis revealed that relatively strong HIF-1α expression in cancer tissues was related to greater invasion (P<0.05), higher tumor pathologic stage (P<0.05), higher American Joint Committee on Cancer (AJCC) stage (P<0.05) and shorter overall survival time (P<0.05). Conversely, HIF-2α staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2α expression in cancer tissues was related to less invasion (P<0.05), lower tumor pathologic stage (P<0.05), lower AJCC stage (P<0.05) and longer overall survival time (P<0.05). Moreover, the HIF-1α(high)/HIF-2α(low) group showed a shorter survival time than the HIF-1α(low)/HIF-2α(high) group. In conclusion, although HIF-1α and HIF-2α mRNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1α and HIF-2α expression might be useful to predict the prognosis of patients with PC.
Subject(s)
Humans , Basic Helix-Loop-Helix Transcription Factors , Genetics , Metabolism , Hypoxia-Inducible Factor 1, alpha Subunit , Genetics , Metabolism , Pancreatic Neoplasms , Metabolism , Pathology , Prognosis , RNA, Messenger , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To assess the neuroprotective effects of ginsenoside Rg1 against β-amyloid peptide (Aβ(25-35))-induced apoptosis in primarily cultured rat cortical neurons.</p><p><b>METHODS</b>Primarily cultured cortical neurons were obtained from embryonic (E18d) rat fetus and maintained in neurobasal medium for 7d. Primary neurons pretreated with 1 μmol/L, 10 μmol/L or 20 μmol/L Rg1 for 24 h were challenged with 10 μmol/L Aβ(25-35) for 72 h. Morphological changes of neurons were evaluated; mitochondrial membrane potential (ΔΨm) was measured; with JC-1 staining and the expression of neural apoptosis-related proteins was detected by Western blot analysis.</p><p><b>RESULTS</b>Exposure to Aβ(25-35) for 72 h caused serious neural cell insults. A pretreatment with Rg1 significantly reduced Aβ(25-35)induced cell death in a dose-dependent manner, with a maximal effect (-90%) obtained at 20 μmol/L. The JC-1 staining results demonstrated the loss of ΔΨm after Aβ(25-35) treatment, while Rg1 maintained the normal level of ΔΨm. A series of mitochondrion-mediated apoptotic events happened after Aβ(25-35) treatment, such as decrease of Bcl-2/Bax, release of cytochrome C and activation of caspase 9 and caspase 3, which were all blocked by Rg1 pretreatment. Both estrogen receptor (ER) antagonist ICI182, 780 and glucocorticoid receptor (GR) antagonist RU486 blocked the antiapoptotic effects of Rg1.</p><p><b>CONCLUSION</b>Ginsenoside Rg1 protects primary cultured rat cortical neurons from Aβ(25-35)-induced injury, which may be associated with mitochondrion-mediated antiapoptosis pathway.</p>
Subject(s)
Animals , Rats , Amyloid beta-Peptides , Toxicity , Apoptosis , Caspase 3 , Metabolism , Caspase 9 , Metabolism , Cells, Cultured , Cerebral Cortex , Metabolism , Pathology , Ginsenosides , Pharmacology , Membrane Potential, Mitochondrial , Mitochondria , Metabolism , Physiology , Neurons , Metabolism , Pathology , Peptide Fragments , Toxicity , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats, Sprague-Dawley , bcl-2-Associated X Protein , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of red clover isoflavones on the proliferation and apoptosis of human benign prostatic hyperplasia (BPH) stromal cells.</p><p><b>METHODS</b>We treated human prostate stromal cells with red clover isoflavones at the concentration of 12.5, 25, 50 and 100 microg/ml, and established a PBS blank control, a dimethyl sulphoxide (DMSO) negative control and four finasteride positive control groups (at the concentration of 12.5, 25.0, 50.0 and 100.0 microg/ml). We determined the effects of different concentrations of red clover isoflavones on the proliferation of the cells by MTT assay and on their apoptosis by Annexin V/PI double staining flow cytometry.</p><p><b>RESULTS</b>Red clover isoflavones inhibited the proliferation of the BPH stromal cells by 18.86% at 25.0 microg/ml, compared with 5.17% in the blank control group (P < 0.05), and more obviously at a higher concentration. At 50.0 microg/ml, red clover isoflavones exhibited a weaker inhibitory effect than finasteride (28% vs 69.88% , P < 0.05). Annexin V/PI double staining flow cytometry showed that red clover isoflavones at 25.0 microg/ml induced the apoptosis of the prostate stromal cells by (18.54 +/- 2.5)%, with significant differences from the negative control and blank control (P < 0.01).</p><p><b>CONCLUSION</b>Red clover isoflavones can inhibit the proliferation and promote the apoptosis of human BPH stromal cells.</p>