Effect of L-arginine on human colon carcinoma cell line LS174 through NO pathway and the mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of L-arginine (L-Arg) on human colon carcinoma cell line LS174 through NO pathway and the mechanism.</p><p><b>METHODS</b>LS174 cells were cultured in the presence of L-Arg at different concentrations for different time. MTT assay was employed to evaluate the cell proliferation, and the cell morphological changes were observed by optical and electron microscopy. The apoptosis of L-Arg-treated cells was observed by the Annexin V/PI staining. The expression levels of VEGF, COX-2, p53, bcl-2 and bax in the cells were determined using Western blotting and immunocytochemical staining.</p><p><b>RESULTS</b>L-Arg promoted the growth of LS174 cells at a low concentration (0.125 mmol/L) and inhibited the cell growth at higher concentrations (0.5, 2, 8, and 32 mmol/L). Under electron microscope, ultrastructual changes in the cytoplasm and nuclei of LS174 cells were observed 48 h after exposure to L-Arg. Some of the cells showed morphological changes characteristic of cell apoptosis such as cell size reduction, condensation and margination of the nuclear chromatin. Low concentration of L-Arg resulted in a cell apoptosis rate of 2.29%, as compared with the rate of 2.84% in the control group; at higher concentrations, L-Arg caused significantly increased cell apoptosis rates to 26.88%, 28.95%, 63.36%, and 84.51%, respectively. In cells treated with a low concentration of L-Arg, the expressions of VEGF and COX-2 were increased as compared with those in the control cells; higher concentrations of L-Arg obviously decreased the expressions of p53 and bcl-2 and increased the expression of bax.</p><p><b>CONCLUSION</b>Low-concentration L-Arg can promote the growth of LS174 cells probably by up-regulating VEGF and COX-2 protein under the influence of NO, the metabolite of L-Arg. The inhibitory effect of high concentrations of L-Arg is probably mediated by inducing cell apoptosis via NO. The mechanism of L-Arg- induced cell apoptosis may be related to the up-regulation of bax protein and the down-regulation of p53 and bcl-2 proteins.</p>

Effect of resveratrol-induced FasL up-regulation on the apoptosis of pancreatic acinar cells in rats with severe acute pancreatitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of resveratrol on the apoptosis of pancreatic acinar cells in rats with severe acute pancreatitis (SAP) and explore the mechanism of such effect.</p><p><b>METHOD</b>SD rats with 3.5% sodium taurocholate-induced SAP were treated with resveratrol, and the serum amylase was detected with automatic biochemistry analyzer. The apoptosis of the pancreatic acinar cells in the rats was detected by TUNEL assay, and the expression of Fas and FasL genes was determined by RT-PCR and Western blotting. The pathological changes of the pancreas were observed under optical microscope.</p><p><b>RESULTS</b>Compared with SAP group, the resveratrol-treated rats showed obviously decreased serum amylase and scores for pancreatic histopathological lesions. Resveratrol treatment significantly increased the apoptotic indices of pancreatic acinar cells and the levels of FasL mRNA and protein in rats with SAP.</p><p><b>CONCLUSION</b>Resveratrol produces important therapeutic effect on SAP in rats by inducing pancreatic acinar cell apoptosis possibly as a result of up-regulated FasL gene expression.</p>

Transcatheter arterial chemoembolization with high-dose iodized oil for hepatic VX2 tumor in rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of transcatheter arterial chemoembolization (TACE) with high-dose iodized oil on hepatic tumor growth and metastasis in rabbits.</p><p><b>METHODS</b>Forty-eight rabbits with implanted VX2 tumor were randomly divided into control group, routine dose iodized oil TACE group and high-dose iodized oil TACE group to receive perfusion through the hepatic artery with 0.9% saline, 5 mg adriamycin with routine-dose iodized oil, and 5 mg adriamycin with high-dose iodized oil, respectively. The tumor volume, tumor necrosis, intrahepatic and lung metastasis were examined 2 weeks after TACE.</p><p><b>RESULTS</b>No significant difference was found in the tumor volume between the 3 groups before TACE (P>0.05). The rabbits receiving TACE with iodized oil, especially at the high dose, showed significantly reduced tumor volume as compared with the control group (P<0.01). TACE with high-dose iodized oil resulted in significantly increased tumor necrosis rate in comparison with the control group and TACE with a routine dose of iodized oil (P<0.05); high-dose iodized oil TACE was also associated with reduced intrahepatic and lung metastasis as compared routine dose iodized oil TACE (P<0.05).</p><p><b>CONCLUSION</b>TACE with high-dose iodized oil can obviously inhibit the growth and intrahepatic and lung metastasis of transplanted VX2 liver tumor in rabbits .</p>

Expression of survivin gene in a rat model of acute pancreatitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of survivin in acute pancreatitis in rats.</p><p><b>METHODS</b>Acute pancreatitis was induced in rats by retrograde injection of sodium taurocholate into the pancreaticobiliary duct. The expressions of survivin in the pancreatic tissues was detected by immunohistochemisty, Western blotting and RT-PCR, and the apoptotic ratio of the acinar cells was determined by TUNEL assay.</p><p><b>RESULTS</b>Survivin was not detected in the control group, and in rat models of acute pancreatitis, the expressions of survivin protein and mRNA increased but the apoptotic index of the acinar cells decreased gradually with the severity of inflammation.</p><p><b>CONCLUSION</b>Survivin is involved in the regulation of acinar cell apoptosis and also the necrosis of the apoptotic acinar cells through its anti-apoptosis activity to aggravate acute pancreatitis, suggesting its value as a promising marker in predicting the severity of acute pancreatitis.</p>

Protective effect of resveratrol on the intestinal mucosal cells in rats with severe acute pancreatitis and the mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of resvertrol on the intestinal mucosal cells in rats with severe acute pancreatitis and explore the possible mechanism.</p><p><b>METHODS</b>Twenty-four SD rats were randomly divided into the sham-operation (SO) group, severe acute pancreatitis (SAP) group and resveratrol-treated (RES) group. In the SO group, the pancreases were slightly flipped only. In the SAP and RES groups, SAP model was established by retrograde injection of 40 g/L sodium chrolate (1 ml/kg) through the pancreatic duct, and in the latter group, resveratrol (10 mg/kg) was given intravenously. Specimens were obtained 6 h after SAP model establishment and the endotoxin levels in the portal vein was determined with turbidimetry to evaluate the effect of resversatrol on the intestinal endotoxin translocation in SAP rats. Apoptosis of the mucosal cells was detected by TUNEL methods, and the expression of bax and bcl-2 mRNA were determined by RT-PCR. The mitochondrial membrane potential of the intestinal mucosal cells was measured by confocal microscopy.</p><p><b>RESULTS</b>The endotoxin levels in the portal vein were significantly lower in RES group than in SAP group (P<0.01). TUNEL assay demonstrated significantly higher apoptotic index of the mucosal cells in SAP group than that in RES group (P<0.01). The expression of Bax mRNA in the intestinal mucosal cell was significantly higher in SAP group than in RES group (P<0.01), whereas the expression of bcl-2 mRNA was significantly lower in SAP group (P<0.01). The mitochondrial membrane potential of the intestinal mucosal cell was significantly lower in SAP group than in RES group (P<0.01).</p><p><b>CONCLUSION</b>Resvertrol can inhibit the apoptosis of the intestinal mucosa cells and maintain the integrity of the intestinal barrier to prevent the bacterial and endotoxin translocation in SAP.</p>

Comparision of different interventional therapies for primary liver cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of different interventional therapies for primary hepatic cell cancer (HCC).</p><p><b>METHODS</b>1126 HCC patients before or after hepatectomy were treated by different kinds of interventional therapies: transcatheter arterial chemoembolization (TACE), TACE and radio-frequency ablation (RFA), Chinese traditional medicine and biotherapy after TACE or the transcatheter arterial infusion (TAI). The results of liver function, alpha-fetoprotein, imaging, color-ultrasonography and survival rate were reviewed.</p><p><b>RESULTS</b>874 patients were followed up for 2 to 63 months. The overall 1-, 3-, 5-year survival rate was 67.8% , 28.7% and 18.8%, respectively. The 1-, 3-, 5-year survival rate of patients who received TACE before hepatectomy was 74.7%, 41.4% and 36.9% ; after hepatectomy 78.9%, 40.4% and 37.5%, respectively. The response rate ( PR + NC) of TACE and RFA was 93.4%, and the 1-, 3-year survival rate was 74.5% and 36.8%, respectively, after TACE and RFA. The response rate (PR + NC) of TACE was 83.2% with 1-, 3-, 5-year survival rate of 69.3%, 21.7%, 8.4% after TACE, respectively. The response rate (PR + NC) of TAI was 27.5% with 1-, 2-year survival rate of 11. 6% and 0 after TAI. The Child grade of liver function, color-ultrasonography and alpha-fetoprotein of TACE + RFA group, TACE and TAI were compared. There was no significant difference between each above mentioned index among TACE, RFA or TACE groups.</p><p><b>CONCLUSION</b>Compared with other modalities, transcatheter arterial chemoembolization (TACE) before or after hepatectomy is more effective than other interventional therapies for primary hepatocellular cancer, whereas, if combined with radiofrequency ablation (TAI), it is much more effective than TACE alone.</p>

Geldanamycin inhibits proliferation and motility of human HER2/neu-overexpressing breast cancer cell line SKBr3 / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the antitumor effect of a benzoquinone ansamycin antibiotic, geldanamycin (GA), against HER2 /neu tyrosine kinase-overexpressing human breast cancer cell line SKBr3.</p><p><b>METHODS</b>To evaluate the antitumor activity of GA, the degradation of HER2 /neu tyrosine kinase in GA-treated SKBr3 cells was analyzed by Western blotting, their proliferation assessed using MTT assay, and the cell cycle distribution identified by flow cytometry. RT-PCR and Real-time PCR were employed to detect cyclin D1 mRNA expression and cell culture inserts model was used to evaluate the motility of the cells.</p><p><b>RESULTS</b>GA induced a dose- and time-dependent degradation of HER2 /neu tyrosine kinase and cell proliferation inhibition. GA treatment obviously decreased the survival rates of the cancer cells, leading also to a dose-dependent G(1) arrest. The antitumor effects of GA proved to be relevant with declined transcription of cyclin D1. The GA-treated cells also exhibited reduced motility.</p><p><b>CONCLUSION</b>GA can efficiently destabilize HER2 /neu tyrosine kinase and inhibit the proliferation and motility of human breast cancer cell line SKBr3 overexpressing HER2 /neu tyrosine kinase.</p>

Effect of resveratrol on lipopolysaccharide-induced activation of rat peritoneal macrophages / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate nuclear factor kappa B (NF-kappaB) activation induced by lipopolysaccharide (LPS) in rat peritoneal macrophages (PMAs) and the inhibitory effect of resveratrol on NF-kappaB activation.</p><p><b>METHODS</b>PMAS from normal SD rats were randomly divided into 7 groups, including a control group, a LPS group and 5 resveratrol groups (I-V). PMAs of the control group were incubated in DMEM, and those in LPS group in DMEM containing LPS (10 microg/ml). PMAS of resveratrol groups I-V were incubated in DMEM containing LPS (10 microg/ml) and different concentrations of resveratrol. After 24 h of incubation, NF-kappaB activation in the PMAs was determined, and the expression levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and nitric oxide (NO) in the culture medium were measured.</p><p><b>RESULTS</b>Exposure to LPS resulted in an excessive enhancement of cytokine and NO expressions in the PMAs. Resveratrol at 1.25-10 microg/ml produced a dose- dependent inhibition of cytokine and NO expressions and on NF-kappaB activation in LPS-stimulated PMAs.</p><p><b>CONCLUSION</b>Resveratrol can inhibit LPS-induced NF-kappaB activation in rat PMAs and subsequently suppress the expressions of TNF-alpha, IL-1 and NO.</p>

Colocalized expression of Fas and Fas-ligand in acute pancreatitis and its correlation with cell apoptosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the expressions of Fas and Fas-Ligand (FasL) genes in rats with acute pancreatitis (AP) and their relation to apoptosis of pancreatic acinar cells.</p><p><b>METHODS</b>Rat models of acute pancreatitis with varied severity were established by retrograde injection of sodium taurocholate at different concentrations via the apancreatobiliary duct. The expressions of Fas and FasL mRNAs and proteins were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The apoptosis of acinar cells was quantified by in situ nick ending-labeling technique.</p><p><b>RESULTS</b>of expressions fas, FasL mRNA and protein were colocalized in normal pancreatic acinar cells. In pancreatic tissue with less severe inflammation, the expressions of Fas and FasL mRNA increased significantly, and the apoptosis index of the acinar cells was also elevated; with the increase in the severity of the pancreatitis, the expression of Fas and FasL mRNAs were gradually lowered and apoptosis index of the acinar cells was increased.</p><p><b>CONCLUSION</b>Fas/FasL system might be involved in the renewal and homeostasis of normal pancreatic tissue, and constitute an important pathway mediating the apoptosis of pancreatic acinar cells in AP.</p>