Objective To study the relationships between expressions of somatostatin receptor subtypes（SSTR1-SSTR5） and angiogenesis in colorectal cancer. Methods The expressions of SSTR1-SSTR5, VEGF, and CD34 in the paraffin sections of colorectal cancer tissues from 127 cases were detected by the standard streptavidin-peroxidase (SP) technique. CD34 was used as a marker to account microvessel density (MVD) in colorectal cancer tissues. The relationships between the expressions of SSTR1-SSTR5 and VEGF expression, or MVD were analyzed. Results The positive expression rate of SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 was 64.6% （82/127）, 36.2% （46/127）, 18.9% （24/127）, 18.9% （24/127）, and 38.6% （49/127） in colorectal cancer tissues, meanwhile, the positive expression rate of VEGF was 63.8% （81/127） and MVD was (34.67±16.62)/HP in colorectal cancer tissues. The positive expression rate of VEGF (47.8%， 22/46) and MVD 〔(29.00±15.32)/HP〕 in colorectal cancer tissues with SSTR2 positive expression were significantly lower than those in colorectal cancer tissues with SSTR2 negative expression 〔72.8%， 59/81； (37.90±16.56)/HP〕, Plt;0.05. There were no relationships between SSTR1, SSTR3, SSTR4, and SSTR5 expression and VEGF expression or MVD （Pgt;0.05）. Conclusion The positive expression of SSTR2 is related with angiogenesis in colorectal cancer tissues.
【Abstract】ObjectiveTo investigate the inhibitory effects of somatostatin analogue (SSTA) on the colonic carcinoma cell growth in vitro and in vivo and its possible mechanism. MethodsThe somatostatin receptor type Ⅱ (SSTR2) mRNA of colonic carcinoma cell line HCT116 was detected by using RTPCR and hybridization in situ. The effects of octreotide (Oct) or NC-8-12 (specific agonist of SSTR2 ) on the proliferation of HCT116 was measured with MTT after HCT116 stimulated by insulin or epidermal growth factor (EGF) and incubated with Oct or NC-8-12 simultaneously for 24 hours. The expression of cyclin D1 was detected with flow cytometry. The HCT116 were implanted in nude mice subcutaneously and treated with Oct or NC-8-12. The tumor volume and tumor weight were measured according to schedule. Results①SSTR2 mRNA was detected in HCT116 and the tumor implanted in nude mice; ②Insulin and EGF increased the proliferation of HCT116 significantly, and this proliferation could be inhibited by Oct and NC-8-12 partially; ③Insulin increased the Cyclin D1 expression of HCT116, its level decreased slightly when treated with Oct or NC-8-12 but not significantly (Pgt;0.05); ④The weight and volume of implanted tumor in nude mice treated with Oct or NC-8-12 showed no significant difference compared with the control group (Pgt;0.05). ConclusionBoth Oct and NC-8-12 could inhibit the proliferation of colonic carcinoma cell line HCT116 in vitro, which indicated that SSTR2 may mediated the inhibition. Oct and NC-8-12 have no effect on the growth of implanted HCT116 in nude mice in this experiment.
【Abstract】ObjectiveTo investigate the inhibitory effects and the mechanisms of octreotide (OCT) on the growth of hepatocellular carcinoma (HCC). MethodsBel7402 HCC cells were studied for proliferative ability by MTT assay, morphology by light microscopy, adhesive and invasive ability by cell adhesion and “wound strack” experiments. Immunofluorescence flow cytometry was used for study of cMet expression and cell cycle as well. Furthermore, the effects of OCT on tumor growth metastasis were investigated in nude mice with implanted HCC. The expression of cMet in implanted tumor cells was studied by immunohistochemistry. ResultsWith OCT treatment, the proliferative ability of Bel7402 cells and cell morphology didn’t change. The adhesive and invasive ability decreased compared with no OCT treatment cells (P＜0.05). The ratio of G0/G1 cells increased markedly (P＜0.05). The proportion of Bel7402 cells expressing cMet was reduced significantly (P＜0.05). The growth of implanted tumor was inhibited with OCT treatment (P＜0.05). The intensity of cMet expression in OCT group was remarkably weaker than that in control group. In addition, no recurrence and metastasis was found in OCT group 7 weeks after curative resection of xenografts, while 3 cases in controd group were observed to have the recurrence and metastasis. The intensity of cMet immunolabeling in the metastatic tumors was higher than that in xenografts of control group, but the difference was not significant. ConclusionOCT inhibits the growth of HCC by downregulation of cMet.
To investigate the origin and releasing relation of motilin (MTL), vasoactive intestinal peptide (VIP) and somatostatin (SS) in guinea pig bile as well as its effects during gallstone formation. Guinea pig were divided into three groups: control group (50 animals), on normal diet; lithogenic group (70 animals), fed with lowprotein low fat; and recovering group (50 animals), fed with lowprotein low fat and recovering normal food after the experiment of gallstone formation. MTL, VIP and SS in the bile gallbladder tissue and portal vein plasma of the normal control group were measured with radioimmunoassay. Meanwhile the changes of the gut peptides in the bile and the bile components from different groups were also compared. Results: In control group the levels of MTL, VIP and SS in the bile were higher than those in the plasma, but, obviously lower than those in the tissues, the concentration relationship between in the bile and in the tissue was a positive correlation. In contrast to the control group, MTL concentration decreased but VIP and SS increased in the bile of the lithogenic group, the physicochemical nature of the bile also became lithogenic. In the recovering group the bile also became lithogenic, but, the concentration of those peptides and the nature of the bile all got normal. Conclusion: MTL, VIP and SS in guinea pig bile originate mainly form the gallbladder wall tissues. Food components affect the levels of the gut peptides in bile, which promote the bile lithogenic changes and gallstone formation.
Objective To systematically evaluate the effectiveness of somatostatin analogs versus placebo for Graves’ ophthalmopathy (GO). Methods Such databases as PubMed, EMbase, The Cochrane Library, WanFang Data, CNKI, VIP and CBM were searched to collect the randomized controlled trails (RCTs) about somatostatin analogs for Graves’ Ophthalmopathy (GO) pulished by March 2012, while the bibliographies of the included literatue were also retrieved. According to the inclusion criteria, two reviewers screened literature, extracted data and assessed the quality of the included studies. Then meta-analysis was conducted using RevMan 5.0 software. Results A total of 5 RCTs involving 210 patients were included. The results of meta-analysis showed that somatostatin analogs could reduce the clinical activity score (CAS) of GO patients (MD=0.58, 95%CI 0.02 to1.13, P=0.04), but the effects in reducing the degree of proptosis (mm) was still unverifiable (MD=0.21, 95%CI –0.14 to 0.56, P=0.24). It did not show obvious effects for diplopia, orbital volume, intraocular pressure, visual acuity or the restriction of eye movements. The existing evidence could not confirm that somatostatin analogs were effective for GO (OR=1.32, 95%CI 0.45 to 3.9, P=0.61). Conclusion Somatostatin analogs can reduce the CAS of GO patients, but without significantly clinical significance. Moreover, the effect of reducing proptosis is sitll unverifiable. So the existing evidence cannot confirm that somatostatin analogs are effective for GO. For the quality and quantity limitation of the included studies, this conclusion needs to be proved by performing more high quality RCTs.
Objective To investigate the regulatory effect of somatostatin analogue (SMS201995,SMS) on proliferation and apoptosis in human cholangiocarcinoma cell line in vitro. MethodsProliferation curve, flow cytometry, agarose gel electrophoresis, Annexin VFITC and flow cytometric immunofluorescent technique were performed to identify the inhibitory effect on cell proliferation and the induction of apoptosis of human cholangiocarcinoma cells (SKChA1). ResultsSMS significantly reduced the SKChA1 cell growth by serum in long experiments and transiently accumulated it in G0/G1 phase. Dotplot analysis of cells duallabeled with Annexin VFITC and PI confirmed the induction of apoptosis by SMS in SKChA1 cells.AnnexinVFITC labeling was markedly enhanced following treatment with SMS for 24 h. DNA of treated SKChA1 cells appeared a ladder pattern characteristic of apoptosis. Besides, timedependent increase in bax and decrease in bcl2 occured during SMS treatment. Conclusion SMS could inhibit the proliferation activity and induce apoptosis of cholangiocarcinoma cell line SKChA1. The mechanisms of apoptosis might be correlated with the expression of apoptosisregulatory gene bax and bcl2.
Objective To investigate the effect of angiostatin gene combined with somastatin on inhibiting proliferation of human pancreatic cancer cell BXPC-3 and endothelial cell of vascular ECV-304 and on inducing their apoptosis in vitro. Methods The pcDNA3/angio was transfected BXPC-3 by liposome-mediated gene transfer method. RT-PCR and Western blot were used to detect the expression of angiostatin gene. In vitro, MTT and flow cytometry (FCM) were used to detect whether angiostatin gene combined with somastatin could effect the growth inhibition of BXPC-3 and ECV-304 cells. Results Angiostatin was expressed and secreted by transfected BXPC-3. The growth of BXPC-3 was inhibited by certain concentration of somatostatin (≥10 μg/ml, P＜0.01）, which was dependent on the dose of somatostatin in a concentration extent; Simultaneity apoptosis was induced （P＜0.01）. But the growth of ECV-304 was not inhibited with somatostation （Pgt;0.05）. Angiostatin could inhibit the growth of ECV-304 and induced apoptosis （P＜0.01）, but it had no effect on the growth of BXPC-3 （Pgt;0.05）. Angiostation gene combined with somatostation could inhibit the growth both of BXPC-3 and ECV-304 （P＜0.01）, and induce apoptosis of them （P＜0.01）; but the effect couldn’t be additived. Conclusions ①Somatostatin directly inhibits the proliferation of human pancreatic cancer cells and induces apoptosis, but it doesn’t directly inhibit angiogenesiso of human pancreatic cancer. ②Angiostatin specially inhibits the proliferation of endothelial cell of vascular and induces apoptosis. Angiostatin could inhibit angiogenesis of human pancreatic cancer to induce necrosis of cancer cell.
ObjectiveTo investigate the effects of somatostatin8 (SS8) on the apoptosis and the expression of cmyc protein of hepatocellular carcinoma cell SMMC7721. MethodsCultured in vitro, hepatocellular carcinoma cells SMMC7721 were incubated with SS8 (10 μg/ml). The apoptosis rate and expression of cmyc protein were detected by flow cytometry (FCM). ResultsSS8 can cause the spanonumber in S and G2/M phase and the auxonumber in G0/G1 phase of SMMC7721 cells . The apoptosis rate was 14.2% in the study group and 6.1% in the control group, and there was significant difference (P＜0.05); The level of expressions of cmyc protein was 0.833±0.035 after action by SS8 for 24 h. Compared with control group, there was no significant difference in the study group（P＞0.10）.But after the cells were incubated with SS8 for 48，72，96，120，144 h, the level of expressions of cmyc protein was 0.818±0.04，0.721±0.029，0.669±0.026，0.648±0.045，0.642±0.028 respectively in the study group, and there was significant difference as compared with the control group (P＜0.05). Conclusion The SS8 can induce the apoptosis and lower expression of cmyc protein of hepatocellular carcinoma cell SMMC7721.
Human SW480 colonic cancer cell line was evaluated for its growth response to Octa peptide somatostatin (SMS 201·995, SMS) in vitro by MTT assay and flow cytometry. The results showed that SMS possessed an inhibitive effect on SW480 cell at dose 1.563－200ng/ml, the maximal effective dose was 50ng/ml. Inhibitive effect of SMS did not steadily increase at a dose ＞50ng/ml. It suggests that effect of SMS is achieved via somatotatin receptor. SMS obviously inhibited the synthesis of DNA and protein, and prohibited the SW480 cell shifting from phase G0/G1 in phase S, G2M, which suggests that somatostatin (SS) possessed an inhibitive effect on large intestinal at cancer cell, it is achieved at receptor by inhibiting the synthesis of DNA and protein and prohibiting cell cycle of cancer.
ObjectiveTo explore the therapeutic effect and its possible mechanisms of somatostatin combined with antibiotics on acute cholecystitis through the detection of serum tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) in rabbits. MethodsForty-five rabbits were randomly averagely classified into three groups following the establishment of acute cholecystitis model: control group, blank group， and experimental group. The rabbits in control group received cefazolin sodium and metronidazoie by intravenous injection twice a day. The rabbits in experimental group got a hypodermic injection of somatostin (20 μg/kg) twice a day besides antibiotics, while these drugs were replaced by equal volume of normal saline for the rabbits in control group. The concentrations of serum TNFα and CRP were detected by enzyme-linked immunosorbent assay and histomorphological and electron microscopic changes of gallbladder in rabbits were observed on 3 d after administer. ResultsThe concentrations of serum TNF-α of rabbits in experimental group 〔(401.6±48.7) pg/ml〕 were significantly lower than those in control group 〔(767.3±67.4) pg/ml〕 and blank group 〔(806.7±61.2) pg/ml〕, P=0.000 and P=0.000, while the difference between the latter two groups was not significant (P=0.196). The concentrations of serum CRP of rabbits in experimental group 〔(16.2±1.1) mg/L〕 were significantly lower than those in control group 〔(55.4±1.2) mg/L〕 and blank group 〔(72.8±8.9) mg/L〕, P=0.000 and P=0.000, and which was higher in blank group compared with control group (P=0.018). The Histopathological results showed that gallbladder wall emerged mulifocality mucosal fluid necrosis, lamina propia hyperemia, bulk neutrophil infiltration and sequent alleviation of reaction in the rabbits of experimental group when compared with the rabbits of blank group and control group. Electron microscopic results demonstrated that the intercellular junction of gallbladder kept relative integrity and the swelling and vacuolar degeneration of mitochondria and endoplasmic reticulum obviously relieved. ConclusionsSomatostatin can significantly reduce the concentrations of serum TNF-α and CRP in the model of rabbits acute cholecystitis, which may protect the mucous membrane of gallbladder from the inflammation reaction.