Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice

AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.

Activation of STAT3 signaling in human stomach adenocarcinoma drug-resistant cell line and its relationship with expression of vascular endothelial growth factor

AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.

Effect of intraarterial chemotherapy on vascular endothelial growth factor expression and microvessel density in carcinoma of the cervix

Objective: To clarify the effect of intraarterial chemotherapy on vascular endothelial growth factor (VEGF) expres- sion and microvessel density (MVD) count in carcinoma of the cervix. Methods: Before intraarterial chemotherapy and after 2–3 weeks of therapy, the expression of VEGF and MVD count in 36 carcinoma tissues of locally advanced cervical cancer were determined by CD34. Results: Before intraarterial chemotherapy and after 2–3 weeks, the expression of VEGF were 75% (27/36) and 30.6% (11/36) respectively, and MVD were reduced obviously (P<0.001). Conclusion:?The intraarterial chemotherapy can reduce the expression of VEGF and MVD, and adjust malignancy of cervical cancer, and cut down the postoperative metastasis.

Effect of electroacupuncture on expressions of VEGF and CD31 in MCAO model rats

Objective： To investigate the effect of electroacupuncture （EA） at Ganshu （BL 18） and Shenshu （BL 23） on vascular endothelial growth factor （VEGF） and platelet endothelial cell adhesion molecule-1 （PECAM-1）/CD31 around the cerebral infarction focus in middle cerebral artery occlusion （MCAO） rats and the possible mechanism, thus to provide a new strategy for the treatment of cerebral ischemic stroke by acupuncture. Methods： A total of 180 healthy male Sprague-Dawley （SD） rats were randomly divided into a sham operation group, a model group, an acupoint group and a non-acupoint group, 45 rats in each group. MCAO model was established using the modified line-embolus method in all rats except for those in the sham operation group; rats in the acupoint group were treated with EA at Ganshu （BL 18） and Shenshu （BL 23）; rats in the non-acupoint group were treated with EA at the control points; rats in other 2 groups were only subjected to bundling without treatment. Ten rats in each group were randomly selected on the 3rd day, the 14th day and the 21st day after acupuncture stimulation to test the neurological function impairment. The expression levels of CD31 and VEGF were also detected. Results： Compared with the model group and non-acupoint group, the neurological function score of the acupoint group was decreased at each time point, and the differences were statistically significant （P〈0.05, P〈0.01）. The expressions of VEGF and CD31 in each group were the lowest on the 3rd day, reached the peak on the 14th day and still remained at high level on the 21st day. And the differences among groups were statistically significant both on the 14th day and the 21st day （P〈0.05, P〈0.01）. Compared with the model group and the non-acupoint group, the expressions of VEGF and CD31 in the acupoint group were increased, and the differences were statistically significant （all P〈0.05）. Conclusion： EA at Ganshu （BL 18） and Shenshu （BL 23） can significantly improve the neurological function score of MCAO model rats, and shows protective effect on cerebral ischemia. The protective mechanism may be related to the up-regulation of CD31 and VEGF expression around the cerebral infarction focus in the MCAO model rats and induction of angiogenesis.

An efficacy analysis of anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to multifocal choroiditis and comparison with wet age-related macular degeneration

Objective： To evaluate the effect of anti-vascular endothelial growth factor （VEGF） on juxtafoveal choroidal neovascularization （CNV） secondary to multifocal choroiditis （MFC） and wet age-related macular degeneration （AMD）. Methods： In this retrospective, comparative study, 20 unique eyes with CNV were divided into two groups： 10 patients affected by MFC and 10 patients diagnosed with wet AMD. They all received local intravitreal （Ivr） injections of ranibizumab, with 6 months of follow-up. Retreatment injections were performed based on findings suggestive of active neovascularization. Results： Significant improvements were observed in the juxtafoveal CNV lesions, and average central macular thickness decreased in both groups following the anti-VEGF therapy （P〈0.05）. The average number of injections used in MFC patients was 1.6, while three injections on average were used in wet AMD patients （Z=-2.844, P=0.009）. Best-corrected visual acuity was significantly improved in MFC patients after anti-VEGF therapy （P〈0.05）, and there was no significant difference in wet AMD patients between before anti-VEGF therapy and 6 months later （P〉0.05）. Conclusions： IVT ranibizumab resulted in good clinical outcomes for juxtafoveal CNV secondary to MFC and wet AMD, but the average number of injections used in MFC was fewer than that used in wet AMD over a 6-month observation period. Compared with the wet AMD group, visual acuity was obviously improved in the MFC group at 6 months.

Effects of electroacupuncture pretreatment on motor function and cerebral blood flow in MCAO model rats

Objective:To observe the effects of electroacupuncture(EA)pretreatment on motor function,cerebral blood flow,cerebral infarction volume,and vascular endothelial growth factor(VEGF)level in middle cerebral artery occlusion(MCAO)model rats.Methods:Twenty-four male Sprague-Dawley rats were randomly divided into a normal group,a model group,and an EA group,with eight rats in each group.The middle cerebral artery ischemia-reperfusion model was established by the suture-occluded method in the model group and the EA group,while not in the normal group.The EA group was pretreated with EA at bilateral Fengchi(GB20)before model preparation,once a day for 30 min each time for a total of 7 d.The changes in the CatWalk gait parameters,modified Bederson neurological deficit score,cerebral blood flow,cerebral infarction volume after ischemia,and VEGF level in the brain tissue of rats in each group were observed.Results:Compared with the normal group,the modified Bederson neurological deficit score in the model group and the EA group increased after modeling(P<0.05),and the CatWalk gait parameters(one-leg stance duration,gait cadence,and gait cycle)were all changed(P<0.05).Compared with the model group,the modified Bederson neurological deficit score in the EA group decreased(P<0.05),and the CatWalk gait parameters improved(P<0.05).Immediately after ischemia,the cerebral blood flow in the normal group was greater than that in the model group and the EA group(P<0.05);after reperfusion,the cerebral blood flow in the EA group was greater than that in the model group(P<0.05).Compared with the normal group,the cerebral infarction volume in the model group and the EA group increased(P<0.05).Compared with the model group,the cerebral infarction volume in the EA group decreased(P<0.05).The expression level of VEGF-positive cells in the rat brain tissue in the model group was higher than that in the normal group(P<0.05),and was higher in the EA group than in the model group(P<0.05).Conclusion:EA pretreatment improves the limb motor function in MCAO model rats,alleviates the symptoms of neurological deficits,promotes the recovery of cerebral blood flow,reduces the cerebral infarction area after MCAO modeling,and increases the VEGF expression in the brain tissue.