转录因子8在肿瘤血管发生过程中作用初探

目的研究转录因子8(TCF8)在肿瘤血管生成过程中的作用。方法通过siRNA转染敲除人脐静脉血管内皮细胞(HUVECs)中的TCF8,通过实时PCR和Weston blot检测转染后的HUVECs中TCF8 mRNA和蛋白的表达情况,并通过体外小管形成实验观察TCF8被敲除后对HUVECs管腔形成能力的影响。结果siTCF8转染HUVECs 72 h后TCF8的RNA和蛋白表达水平siTCF8组明显低于sicontrol组(P<0.05);体外小管形成实验显示siTCF8组形成后的多数管腔不完整,其完整管腔数量形成明显少于sicontrol组(P<0.05)。结论应用RNA干扰技术可有效干扰TCF8的表达,敲除TCF8可以抑制肿瘤血管形成,TCF8有可能成为临床上抗肿瘤血管生成治疗的新靶点。     

重组人血管内皮抑制素抑制内皮细胞血管生成的实验研究

目的:观察国产重组人血管内皮抑制素(Endostar,恩度)对人脐静脉内皮细胞(HUVECs)的抗血管生成作用,并对其机制进行初步探讨.方法:采用MTS/PMS系统测定不同浓度恩度对HUVECs和人肝癌细胞株HepG2的生长抑制作用;流式细胞术检测恩度在相同时间内诱导HUVECs和HepG2细胞早期凋亡和晚期凋亡情况;通过迁移/侵袭实验、体外管腔形成实验和鸡胚尿囊膜(CAM)实验观察恩度对HUVECs迁移/侵袭和体内外管腔形成及功能的影响.结果:不同浓度的恩度持续作用72h,对HUVECs具有抑制增殖,且在50～200ng/ml的剂量范围内呈现浓度依赖关系;而对HepG2细胞未见明显作用.药物处理方式的不同,恩度对HUVECs诱导凋亡和迁移/侵袭作用差异显著;对HepG2细胞的迁移/侵袭未见明显影响.高剂量的恩度对HUVECs体外管腔形成和鸡胚尿囊膜的血管发生及成熟具有显著影响.结论:重组人血管内皮抑制素(恩度)能够有效地抑制血管内皮细胞形成复杂的管腔,并显著影响血管的成熟;对人肝癌细胞系HepG2生长及迁移/侵袭未见明显影响.     

高通量肿瘤血管新生研究技术平台的建立

目的：建立高通量肿瘤血管新生研究的体内外技术平台。方法：以VEGF,hFGF为血管新生因子,以Thalidomide血管新生抑制因子对体外培养的血管内皮细胞系（RF／6A,SVEC）应用MTT试验,迁移试验,浸润试验和管状形成试验检测内皮细胞的各种特性;体内实验以鸡胚C57BL／6小鼠为实验动物检测血管新生因子和抑制因子在体内对血管新生的影响。结果：VEGF和bFGF在体内和体外均有促进血管新生的作用,体外试验表明VEGF和bFGF对内皮细胞的增殖活性,迁移、浸润和管状结构形成均有明显的促进作用（P＜0．01）;小鼠体内栓子试验和鸡胚绒毛尿囊膜试验结果均表明,VEGF和b FGF对体内血管新生同样具有促进或刺激作用,和阴性对照组相比主要表现在新生血管密度高、管腔大、管壁完整等;而Thalidomide在体内外均有明显抑制血管新生的作用。结论：本技术平台是一个高通量、经济、简便易行、实用的血管新生研究技术平台。     

重楼醇提物体外抑制血管生成作用研究

目的：探讨重楼醇提物对体外血管生成的抑制作用及其可能的机制。方法：采用MTT法观察重楼醇提物对人脐静脉血管内皮细胞（HUVEC）、人肠癌LOVO细胞增殖的影响。利用transwell小室趋化实验、体外管腔形成实验观察重楼醇提物对HUVEC迁移、成血管能力的影响。结果：重楼醇提物在（15—60）μg／ml浓度范围内，内皮细胞抑制率在24．2％-82．1％之间，具有抑制血管内皮细胞增殖作用；体外管腔形成实验发现，（15—60）μg／ml的重楼醇提物管腔形成数目减少，且管腔不完整，与对照组相比有显著性差异（P分别为0．0000011、0．0000417、0．0008752）。经（15—60）μg／m1的重楼醇提物处理后内皮细胞迁移数明显少于对照组（P分别为0．0000005、0．0000033、0．009993）。而在该浓度范围内，对人肠癌LOVO细胞无明显细胞毒作用（细胞抑制率在12．1％-13．9％之间）。（15—60）μg／ml的重楼醇提物可诱导内皮细胞凋亡，抑制内皮细胞DNA的合成，且呈剂量依赖性（相关系数分别为0．929、-0．922，P为0．036、0．039）。结论：重楼醇提物在体外能有效抑制血管生成。其机制可能与抑制内皮细胞增生、迁移和管腔形成，诱导内皮细胞凋亡，抑制内皮细胞DNA的合成有关。     

Arresten抑制HUVEC细胞增殖和管腔形成的实验研究

目的:探讨血管生成抑制因子arresten对人脐静脉内皮细胞HUVEC增殖和体外血管腔形成的影响,了解其抑制血管生成的途径。方法:采用MTT比色法,观察不同浓度的arresten对HUVEC细胞增殖的影响;Matrigel胶体外管腔形成试验检测arresten对HUVEC细胞形成血管的影响。结果:MTT比色法显示,arresten对HUVEC细胞增殖具有抑制作用,随着浓度的增加,arresten对HUVEC细胞增殖抑制作用也增强,但当其浓度增加到800 ng/mL后其增殖抑制率不再提高; arresten浓度为0、400及800 ng/mL时,HUVEC细胞形成的血管腔数分别为17±2、9±1及5±1。结论:Arresten能够抑制HUVEC细胞的增殖,并抑制HUVEC细胞形成血管腔。     

鼻咽癌肿瘤干细胞分化过程中促血管生成相关因子的表达及其对血管生成细胞的影响

摘要：目的探讨IL-6作为鼻咽癌复发治疗靶点的可行性。观察鼻咽癌肿瘤干细胞分化初期促血管生成相关因子的表达情况及其对血管生成细胞克隆形成的影响。方法本研究首先采用ELISA检测鼻咽癌肿瘤干细胞分化初期细胞因子IL-6及血管内皮生长因子VEGF的分泌情况;进而采用Real time PCR和Western blot技术对比IL-6干扰前后HIF-1α、STAT3、VEGF的转录和翻译水平,并采用平板克隆形成技术检测不同处理组细胞上清液对人脐静脉内皮细胞（HUVECs）克隆形成能力的影响。结果分化初期的鼻咽癌肿瘤干细胞与未分化细胞及普通鼻咽癌细胞CNE-2细胞株比较,具有更强的分泌IL-6及VEGF的能力,且IL-6、HIF-1α、STAT3、VEGF在转录和翻译水平都有较高表达;利用RNA干扰技术沉默IL-6基因表达后,能够明显降低HIF-1α、STAT3、VEGF的表达;分化初期的鼻咽癌肿瘤干细胞上清液较未分化细胞上清液具有更强的促HUVECs细胞平板克隆形成能力,而在鼻咽癌肿瘤干细胞分化初期沉默IL-6基因后所得到的细胞上清液的促HUVECs细胞克隆形成能力明显降低。结论IL-6可作为鼻咽癌发生发展的一个治疗靶点,为临床提供治疗参考。在鼻咽癌肿瘤干细胞分化初期促血管生成因子表达升高并且具有较强的促血管生成能力。     

乳腺癌转移抑制基因1对卵巢癌细胞血管生成的影响及其机制探讨

目的探讨乳腺癌转移抑制基因1(breast cancer metastasis suppressor 1,BRMS1)对人卵巢癌细胞OVCAR3诱导血管内皮细胞形成管腔能力的影响及可能的机制。方法应用脂质体介导的方法将BRMS1 shRNA重组质粒转染人卵巢癌细胞OVCAR3,经G418筛选获得稳定转染株。荧光定量PCR和Western blot法检测BRMS1 mRNA和蛋白的表达水平;体外血管形成实验检测OVCAR3诱导人脐静脉内皮细胞(HUVECs)的血管形成能力;Western blot法检测生长抑制因子4(ING4)和白细胞介素-6(IL-6)的蛋白表达情况。结果稳定转染BRMS1 shRNA后,OVCAR3细胞BRMS1的表达在 mRNA和蛋白水平均受到明显抑制。体外血管形成实验提示,BRMS1表达下调后能显著促进卵巢癌细胞诱导的HUVECs形成管腔样结构的能力;Western blot法显示干扰组中ING4蛋白表达量较对照组下降30%,而IL-6蛋白表达上调,是空白对照组的1.5倍,差异有统计学意义(P<0.05)。结论干扰BRMS1基因的表达可促进卵巢癌细胞诱导血管形成能力,其机制可能与调节下游基因ING4和IL-6的表达有关。     

石见穿有效部位对血管内皮细胞生物学行为的影响

目的:探讨石见穿氯仿及乙酸乙酯部位在体外对血管内皮细胞生物学行为的影响。方法:培养人脐静脉内皮细胞(HUVEC)至3-6代,采用MTT实验、Transwell小室迁移实验、体外小管形成实验观察石见穿氯仿及乙酸乙酯部位对HUVECs体外增殖、迁移、小管形成能力的影响。结果:3.125-25μg/ml的石见穿氯仿部位及乙酸乙酯部位作用于HUVEC 48h,增殖抑制率分别为17.36%-53.08%、9.53%-31.36%,而作用于人肺癌细胞A549增殖抑制率分别为7.10%-31.18%、2.24%-21.69%,两者相比有明显差异细胞毒作用(P=0.001)。3.125-25μg/ml的石见穿氯仿及乙酸乙酯部位作用HUVECs 12h后,迁移抑制率分别为5.39%-57.38%、1.92%-37.37%。3.75-25μg/ml石见穿氯仿部位作用24h时HUVEC小管形成数目减少且管腔不完整,相同浓度石见穿乙酸乙酯部位抑制作用较弱。结论:石见穿氯仿部位抑制内皮细胞增殖、迁移和小管形成作用明显优于乙酸乙酯部位,为石见穿发挥抗血管生成的主要作用部位。     

胶质瘤干细胞血管生成拟态现象的体外研究

背景与目的：血管生成拟态是存在于恶性肿瘤中的,由肿瘤细胞而不是内皮细胞围成的管腔样结构,管腔中有血液流通并参与肿瘤微循环。我们采用体外三维培养模型来观察对比不同来源的胶质瘤干细胞血管生成拟态现象。方法：采用悬浮克隆球形成法诱导获得胶质瘤干细胞,应用胶质瘤干细胞相关分子标记免疫荧光技术鉴定及胶质瘤干细胞裸鼠移植成瘤试验证实已诱导获取的胶质瘤干细胞;采用体外三维培养模型来观察胶质瘤干细胞体外形成血管生成拟态现象。结果：成功获取6种不同来源的胶质瘤干细胞：GSC-1、GSC-2（来源于临床胶质母细胞瘤标本）和SKMG-4G、SKMG-1G、SF-295G、SF-767G（分别来源于胶质瘤细胞系SKMG-4、SKMG-1、SF-295、SF-767）。体外三维培养模型中,拟态管腔分圆形、多边形和三角形3种。GSC-1和SKMG-4G能形成典型的拟态管腔;SKMG-1G和SF-295G只能形成过渡性的非典型的拟态管腔;而GSC-2和SF-767G不能形成拟态管腔。结论：不同来源的胶质瘤干细胞拟态血管形成的能力不同,形态也各异。     

ING4对缺氧状态下血管内皮细胞增殖、迁移及HIF-1α表达的抑制作用

目的:在缺氧状态下,观察ING4对血管内皮细胞增殖、迁移及血管形成相关因子VEGF、MMP-2、MMP-9活性的影响,并探讨ING4对HIF-1α的调控作用。方法:人脐静脉内皮细胞HUVECs体外培养,构建ING4质粒及干扰RNA转染至HUVECs,应用CoCl2处理细胞模拟缺氧环境,MTT法检测细胞增殖,Transwell实验检测细胞迁移,Real time PCR及Western blot实验检测血管形成相关因子VEGF、MMP-2、MMP-9、HIF-1α及其靶基因AK3的mRNA及蛋白表达水平。结果:MTT及Transwell实验结果显示在缺氧状态下,转染ING4质粒能够抑制人脐静脉内皮细胞株HUVECs的增殖及迁移,而转染ING4 siRNA则能够促进HUVECs增殖及迁移,Real time PCR及Western blot实验结果显示转染ING4质粒能够抑制血管形成相关因子VEGF、MMP-2、MMP-9 mRNA及蛋白的表达水平,并且能够抑制HIF-1α及其靶基因AK3的表达水平。结论:在缺氧状态下,ING4能够通过抑制血管内皮细胞的增殖及迁移能力,下调血管形成相关因子VEGF、MMP-2、MMP-9的表达水平,进而抑制新血管形成,其机制可能与ING4能够下调缺氧状态下HIF-1α及其靶基因AK3的表达水平有关。     

Crosstalk between H1975 tumor cells and platelets to induce the proliferation,migration and tube formation of vascular endothelial cells

Activated platelets (PLTs) participate in the regulation of tumor angiogenesis, and tumors can activate PLTs. Whether co-culture of lung carcinoma with PLTs improves the function of human umbilical vein endothelial cells (HUVECs) requires further investigation. The present study aimed to investigate the impact of H1975 cell crosstalk with PLTs on the proliferation, migration and tube formation of HUVECs. Following generation of cell-derived supernatants and construction of the co-culture system, Cell Counting Kit-8, flow cytometry, transmission electron microscopy and a meter for epithelial measurement were performed to detect the proliferative ability of HUVECs. Furthermore, the wound healing and Transwell migration assays were performed to detect the migratory ability of HUVECs. A tube formation assay was performed to assess angiogenesis, ELISA was applied to detect the content of vascular endothelial growth factor (VEGF) and western blotting was carried out to measure the expression levels of VEGF receptor 2 (VEGFR2) in HUVECs. Compared with single-cultured HUVECs (control), co-culture with H1975 cells and PLTs (Exp_HP) improved cell proliferation, increased the proportion of cells in the S-phase, destroyed the cell ultrastructure and decreased transepithelial electrical resistance in HUVECs. In addition, a higher relative migration rate, greater number of migrated cells, stronger tube-forming ability and increased expression of VEGF and VEGFR2 were detected in the Exp_HP group compared with the control group. The properties of HUVECs in Exp_H (co-cultured with H1975 cells) were similar to those in Exp_HP, but significantly weaker. Taken together, the results of the present study suggest that tumor cells interacting with PLTs may play an important role in tumor angiogenesis by affecting or mediating changes in the properties of vascular endothelial cells (VECs).     

Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are well-known factors that induce neovascularization in many tumors. The molecular mechanisms that regulate tumor angiogenesis in human chondrosarcoma are not clear. We assessed in this work the angiogenic activities of a human chondrosarcoma cell line (OUMS-27) in vivo and determined the efficacies of angiogenic factors derived from OUMS-27 cells on human umbilical vein endothelial cells (HUVECs) in vitro. Tumor xenografts induced an increase in the formation of neovessels, but the distributions of Ki-67 antigen, VEGF and bFGF were unaffected. We also demonstrated that OUMS-27 cells secreted VEGF(165) into the culture medium and that it was the maximal angiogenic factor to stimulate endothelial proliferation and migration in chondrosarcoma. Anti-VEGF antibodies induced an approximately 70% inhibition of these responses of HUVECs, but did not have any effect on OUMS-27 cells. Anti-bFGF antibodies suppressed not only the activities of HUVECs but also the growth of tumor cells in vitro. We indicate that angiogenesis is principally elicited by VEGF(165) and that tumorigenesis is mainly regulated by bFGF stored in the extracellular matrix of OUMS-27 cells. The present study may offer the availability of combination therapies for inhibition of VEGF and bFGF action on vascular endothelial cells and chondrosarcoma cells, respectively.     

CXCL12–CXCR7 axis is important for tumor endothelial cell angiogenic property

We reported that tumor endothelial cells (TECs) differ from normal endothelial cells (NECs) in many aspects, such as gene expression profiles. Although CXCR7 is reportedly highly expressed in blood vessels of several tumors, its function in TECs is still unknown. To investigate this role, we isolated TECs from mouse tumor A375SM xenografts, and compared them with NECs from normal mouse dermis. After confirming CXCR7 upregulation in TECs, we analyzed its function using CXCR7 siRNA and CXCR7 inhibitor; CCX771. CXCR7 siRNA and CCX771 inhibited migration, tube formation and resistance to serum starvation in TECs but not in NECs. ERK1/2 phosphorylation was inhibited by CXCR7 knockdown in TECs. These results suggest that CXCR7 promotes angiogenesis in TECs via ERK1/2 phosphorylation. Using ELISA, we also detected CXCL12, a ligand of CXCR7, in conditioned medium from TECs, but not from NECs. CXCL12 neutralizing antibody significantly inhibited TEC random motility. VEGF stimulation upregulated CXCR7 expression in NECs, implying that VEGF mediates CXCR7 expression in endothelial cells. A CXCR7 inhibitor, CCX771 also inhibited tumor growth, lung metastasis and tumor angiogenesis in vivo. Taken together, the CXCL12–CXCR7 autocrine loop affects TEC proangiogenic properties, and could be the basis for an antiangiogenic therapy that specifically targets tumor blood vessels rather than normal vessels.     

Production of VEGF165 by Ewing's sarcoma cells induces vasculogenesis and the incorporation of CD34+ stem cells into the expanding tumor vasculature

The Ewing's sarcoma cell line TC71 overexpresses vascular endothelial growth factor isoform 165 (VEGF165), a potent proangiogenic molecule that induces endothelial cell proliferation, migration, and chemotaxis. CD34+ bone marrow stem cells can differentiate into endothelial and hematopoietic cells. We used a transplant model to determine whether CD34+ cells migrate from the bone marrow to Ewing's sarcoma tumors and participate in the neovascularization process that supports tumor growth. We also examined the role of VEGF165 in CD34+ cell migration. Human umbilical cord CD34+ cells were transplanted into sublethally irradiated severe combined immunodeficient mice. Seven days later, the mice were injected subcutaneously with TC71 tumor cells. Tumors were excised 2 weeks later and analyzed by immunohistochemistry. The tumor sections expressed both human VE-cadherin and mouse CD31, indicating involvement of donor-derived human cells in the tumor vessels. To determine the role of VEGF165 in the chemoattraction of CD34+ cells, we generated two VEGF165-deficient TC71 clones, a stable anti-sense VEGF165 cell line (Clone 17) and a VEGF165 siRNA-inhibited clone (TC/siVEGF(7-1)). The resulting VEGF165-deficient tumor cells had normal growth rates in vitro, but had delayed growth when implanted into mice. Immunohistochemical analysis revealed decreased infiltration of CD34+ cells into both VEGF165-deficient tumors. These data show that bone marrow stem cells contribute to the growing tumor vasculature in Ewing's sarcoma and that VEGF165 is critical for the migration of CD34+ cells from the bone marrow into the tumor.     

褪黑素对肺癌A549细胞诱导的血管内皮细胞增殖的影响

目的探讨褪黑素在体外共培养条件下对肺腺癌A549细胞诱导血管内皮细胞增殖的影响及相关机制。方法建立肺腺癌A549细胞和人脐静脉内皮细胞（HUVECS）ECV-304共培养模型,实验共分成四组：Con组(对照组),nM组(褪黑素终浓度1 nM/L),μM组(褪黑素终浓度1 μM/L),mM组(褪黑素终浓度1 mM/L)。采用BrdU法观察不同浓度褪黑素对血管内皮细胞（ECV-304）增殖的影响,细胞迁移实验观察褪黑素对血管内皮细胞活力的抑制作用,ELISA法检测褪黑素对肺腺癌细胞VEGF蛋白表达的影响。结果低浓度的MLT(1 nM/L)对HUVECs增殖无明显影响,但高浓度 MLT(1 mM/L)明显抑制HUVECs增殖,并有浓度依赖倾向; 高浓度的褪黑素明显降低肺腺癌A549细胞培养液中VEGF的表达。 结论高浓度的褪黑素可以抑制肺腺癌细胞诱导的血管内皮细胞的增殖及迁移,其作用机制可能与褪黑素抑制肺腺癌细胞VEGF的表达有关。     

Upregulation of adipocyte enhancer‐binding protein 1 in endothelial cells promotes tumor angiogenesis in colorectal cancer

Tumor angiogenesis is an important therapeutic target in colorectal cancer (CRC). We aimed to identify novel genes associated with angiogenesis in CRC. Using RNA sequencing analysis in normal and tumor endothelial cells (TECs) isolated from primary CRC tissues, we detected frequent upregulation of adipocyte enhancer‐binding protein 1 (AEBP1) in TECs. Immunohistochemical analysis revealed that AEBP1 is upregulated in TECs and stromal cells in CRC tissues. Quantitative RT‐PCR analysis showed that there is little or no AEBP1 expression in CRC cell lines, but that AEBP1 is well expressed in vascular endothelial cells. Levels of AEBP1 expression in Human umbilical vein endothelial cells (HUVECs) were upregulated by tumor conditioned medium derived from CRC cells or by direct coculture with CRC cells. Knockdown of AEBP1 suppressed proliferation, migration, and in vitro tube formation by HUVECs. In xenograft experiments, AEBP1 knockdown suppressed tumorigenesis and microvessel formation. Depletion of AEBP1 in HUVECs downregulated a series of genes associated with angiogenesis or endothelial function, including aquaporin 1 (AQP1) and periostin (POSTN), suggesting that AEBP1 might promote angiogenesis through regulation of those genes. These results suggest that upregulation of AEBP1 contributes to tumor angiogenesis in CRC, which makes AEBP1 a potentially useful therapeutic target.     

汉防己甲素抑制血管生成的作用

背景与目的:血管生成在肿瘤从良性向恶性转变、癌细胞进入血液循环、转移灶发展和破裂中都起着重要作用.本研究探讨汉防己甲素对体外、体内血管生成的抑制作用及其可能的机制.方法:采用M1_r法观察汉防己甲素对人脐静脉血管内皮细胞(human umbilical vein endothelial cell HUVEC)和人肠癌LoVo细胞增殖的影响.通过Transwell小室趋化实验、体外小管形成实验观察汉防己甲素对HUVEC迁移、成血管能力的影响.建立裸鼠kIVo细胞皮下移植瘤模型.给予汉防己甲素灌胃,观察用药对肿瘤微血管密度的影响.结果:2-8 μg/mL的汉防己甲素作用48 h时对HUVEC的细胞增殖抑制率为24.6%-76.9%,对LoVo细胞增殖抑制率为11.6%～14.0%;体外小管形成实验发现.2～8 μg/mL的汉防己甲素作用24 h时HUVEC小管形成数目减少,且管腔不完整,与对照组比较差异有统计学意义(P值均＜0.001).经2-8 μg/mL的汉防己甲素处理12 h后HUVEC迁移数明显少于对照组(P值均＜O.001).在裸鼠皮下移植瘤体内实验中,80 mg/kg汉防己甲素作用于裸鼠LoVo细胞皮下移植瘤后其微血管密度与生理盐水对照组比较.差异具有统计学意义(p0.035).结论:汉防己甲素在体外能有效抑制血管生成,其机制可能与抑制HUVEC增生、迁移和小管形成,诱导HUVEC凋亡,抑制HUVEC DNA的合成有关.汉防己甲素在体内对裸鼠LoVo移植瘤具有抗血管生成作用.     

重组人血管内皮抑素对血管新生的影响研究

目的 探讨重组人血管内皮抑素（Endostar,恩度）对血管内皮细胞趋化、迁移、粘附、增殖及小管形成等与血管新生相关生物学行为的影响。方法 以原代培养的人脐静脉内皮细胞（HUVEC）为细胞模型,通过Boyden小室荧光定量分析、划痕试验、HUVEC荧光定量粘附分析、CFSE染色流式细胞术、CCK-8定量检测、小管形成试验和Matrigel栓试验研究恩度对HUVEC与血管新生相关的生物学行为的影响。结果 恩度在5～50 000ng／ml范围内可抑制血管内皮生长因子诱导HUVEC的迁移运动,且浓度为50ng／ml和500ng／ml时效果最明显;恩度在5～50 000ng／ml间可呈剂量依赖的方式抑制HUVEC向损伤部位的迁移。与0ng／ml相比,50、500和5000ng／ml 恩度处理的HUVEC的粘附率、增殖率及HUVEC形成网状小管结构的数量、面积和长度均降低,差异均有统计学意义（P＜0.05）; Matrigel栓实验结果显示,恩度在50～5000ng／ml间对SCID小鼠体内血管新生有明显的抑制作用。结论 恩度在细胞水平能抑制HUVEC与血管新生相关的生物学行为,包括HUVEC的趋化、迁移、粘附、增殖和小管形成;在动物水平能抑制SCID小鼠体内的血管新生,据此推断恩度能抑制血管新生。     

血管内皮生长因子的表达对人胃癌细胞生物学表型的影响

 目的　探讨血管内皮生长因子对人胃癌细胞生物学表型的影响。方法　将 VEGF16 5正、反义 RNA表达载体导入人胃癌细胞 ,并观察其细胞周期、增殖、裸鼠致瘤生长等生物学指标。结果　与 VEGF正义转染细胞相比 ,在反义转染细胞的细胞周期中 G1期细胞数增加了 1 7.3% ,而S期细胞减少了 43.6 % ;正义转染细胞的克隆形成率明显高于反义转染细胞 ;正义转染细胞组的肿瘤生长速度及瘤体积明显高于其他组。结论　 VEGF可以加强肿瘤组织血管生成 ;VEGF反义RNA可以防治肿瘤生长 ;VEGF可能与肿瘤细胞增殖能力有关.