【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.
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.
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.
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 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.
ObjectiveTo detect the effect of adeno-associated-virus induced Kringles5 gene on retinal neovascularization in rats with retinopathy of prematurity (ROP), and to explore the new ways of treatment for ROP.MethodspSNAV-Kringle5-gfp carrier was constructed by subclone and adeno-associated-virus was packed to form rAAV-Kringle5-gfp. ROP model was set up under circumstances of high oxygen in 21 SD rats which were divided into experimental (21 eyes) and control group (21 eyes). Eighteen eyes from each group was used to making the histologic section of retina, and the other 3 eyes in each group was detected by polymerase chain reaction (PCR) and Western blotting. There were 5 rats in the normal control group. AAV-Kringle5-gfp with the dosage of 10 μl and titer of 2.5×1012vg/ml was injected into the eyes in experimental group, while rAAVlacZ with the same dosage and titer of 2.5×1011vg/ml was injected in to the eyes in control group. The expression of target gene in ocular tissues was observed under the fluoroscope. Twelve weeks later, the rats were executed, and the staining of Ⅷ factor related antigens in retinal vascular endothelial cells was performed and number of nucleolus of vascular endothelial cells were counted. ResultsThe plasmid of pSNAV-Kringle5-gfp was correct according to the sequence measurement; the expression of rAAV-Kringle5-gfp was found in vitreous cavity and on retina; the expression of target gene was found on the level of mRNA and protein; the number of nucleolus of vascular endothelial cells on the surface of retina was (19.954 2±3.825 7) in experimental group and (7.335 2±2.731 3) in the control group, which had significant difference between the two groups (P＜0.01）.ConclusionsAdeno-associated-virus induced Kringles5 gene can inhibit the occurrence of retinal neovascularization in patients with ROP.(Chin J Ocul Fundus Dis, 2005,21:288-291)
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.
The somatostatin levels in serum, cancer tissue and its adjacent mucosas were measured in 43 patients with large intestine carcinoma(LIC). The results showed that the somatostatin level in serum of patients with LIC before operation was obviously lower than that in the control group (Plt;0.001)and after radical operation, it was markedly higher than the preoperative levels(Plt;0.01), but still lower than the control value(Plt;0.001). The somatostatin level in cancer tissue was evidently lower than that in its adjacent mucosas(Plt;0.001)and in normal mucosa(Plt;0.001). There was no significant correlation between the somatostatin level in serum or carcinoma tissue and Duke’s stage or pathological types of the carcinoma tissue. The results indicate that the somatostatin has a negative modulating effect on the growth of large intestine carcinomas, thus provides an experimental basis for the treatment of large treatment of large intestine carcinomas with drugs such as somatostatin.
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 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.