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.
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.
The model of transplanted colonic SW480 cell line carcinoma in gymnomouse body was set up to observe the effect of octapeptide somatostatin (SMS 201-995,SMS) on the transplanted carcinoma and elucidate its mechanism. Results: the volume, weight, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G2M phase in SMS group and SMS+PG (pentagastrin) group were markedly lower than those in PG group and control group, those of PG group were markedly higher than those in control group.The cell amount of G0/G1 phase in SMS group and SMS+PG group was markedly higher than that in PG group and control group, and that of PG group was markedly lower than that in control group.All these suggested that somatostatin could not only inhibit the growth of transplanted human colonic SW480 cell line carcinoma directly but also inhibit the growthpromoting effect of gastrin on the transplanted carcinoma.The mechanism might be that somatostatin inhibit the synthesis of cAMP, DNA and protein in carcinoma cells, then inhibit the cell growing from G0/G1 phase to S and G2M phases.Our study might provide experimental basis for the homonotherapy with analogue of somatostatin in patients with large intestine carcinoma.
ObjectiveTo investigate the role of somatostatin in gastrointestinal function after operation for treatment of abdominal injury patients. MethodsSixty patients with abdominal trauma were divided into somatostatin in treatment group (n=30) and the conventional treatment control group (n=30). The amount of gastrointestinal decompression drainage, bowel sounds recovery time, exhaust time, defecation time, and the levels of serum C reactive protein, TNF-α, IL-6, and IL-8 after operation in two groups were observed. ResultsSomatostatin treatment group recovery time of bowel sounds, exhaust time, and defecation time were earlier than the control group, hospitalization time shortened, and the amount of gastrointestinal decompression drainage reduced (P < 0.05), The levels of serum C reactive protein, TNF-α, IL-6 and IL-8 of somatostatin treatment group were lower than those in control group (P < 0.05), and the magnitude of decline above index in the somatostatin treatment group were greater than that in the control group (P < 0.05). ConclusionSomatostatin can promote the recovery of gastrointestinal function in patients after operation in abdominal injury.
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 evaluate the effectiveness and safety of somatostatin and the analogue-octreotide in preventing post-ERCP pancreatitis. Methods We searched Cochrane Clinical Trial Register （Issue 1, April, 2004 ）, MEDLINE （1966- April, 2004）, EMBASE （1985- April, 2004）, CBM disc （1970- April, 2004） and The Clinical Trial Register of Chinese Evidence-Based Medicine Center and handsearched the related journals to identify Randomized Controlled Trials （RCT）of somatostatin and octreotide in post-endoscopic retrograde chnlangiopancreatography pancreatitis（PEP）prevention. Systematic review was conducted using the method recommended by The Cochrane Collaboration. Results Thirty-one trials involving 4 728 patients undergoing ERCP were included. Meta-analysis showed that the incidence of post-ERCP pancreatitis [ OR 0.33, 95% CI 0. 20 to 0. 54; P =0. 000 01 ; NNT =13] was significantly reduced by somatostatin. Octreotide could only reduce the incidence of hyperamylasemia [ OR 0. 54, 95% CI 0. 38 to 0. 77 ; P =0. 000 7 ]. The inci- dence of PEP, severe PEP and post-ERCP abdominal pain could not be reduced by octreotide. Conclusions Somatostatin can prevent post-ERCP pancreatitis. Four trials are of high quality in the 12 included studies and the results are consistent with the sensitive-analysis, so it is credible to some extent. However, existing evidence does not support that octreotide can reduce the incidence of PEP, so it is not recommended for this indication. Sensitive-analysis even showed that octreotide could increase the incidence of PEP. Therefore, whether it is necessary to carry out further clinical trials should be considered with caution.
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.
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.
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.