siRNA沉默VEGF基因对肾癌细胞增殖与凋亡的影响

目的：探讨siRNA干扰血管内皮生长因子（VEGF）基因对人肾细胞癌细胞株（ACHN）细胞增殖与凋亡的影响.方法：化学合成针对VEGF的小干扰RNA,通过脂质体转染至ACHN中,利用Western印迹法检测细胞内VEGF的表达,采用台盼蓝拒染法测定细胞生长曲线,用MTT比色分析法检测细胞增殖抑制率（IR）,用TUNEL方法检测细胞凋亡率（AR）.结果：生长曲线提示,与空白对照组及阴性对照组相比,siRNA1组、siRNA2组ACHN细胞的生长明显减慢 在24 h、48 h、72 h,siRNA1的增殖抑制率为10.6%、18.0%、27.1%,siRNA2增殖抑制率为18.9%、32.7%、40.3%,均高于空白对照组及阴性对照组（P〈0.05） siRNA1组的细胞凋亡率为10.7%、15.2%、20.3%,siRNA2组的细胞凋亡率为17.3%、26.2%、37.4%,均高于空白对照组及阴性对照组（P〈0.05） siRNA1组、siRNA2组VEGF蛋白表达水平明显低于空白对照组及阴性对照组,其中siRNA2对ACHN细胞的IR、AR和VEGF蛋白表达的抑制作用均显著高于siRNA1组（P〈0.05）.结论：VEGF在肾癌的发生发展中起着重要作用,化学合成的VEGF-siRNA能特异性抑制肾细胞癌ACHN细胞株中VEGF的表达,抑制细胞生长增殖,促进细胞凋亡.对于VEGF基因高表达的肾细胞癌患者,针对VEGF的RNAi技术有望成为肾细胞癌新的基因治疗手段.     

VEGF与肾坌田胞癌研究进展

血管内皮生长因子（VEGF）通过其特异性受体（VEGFR）发挥生物学功能,在肾细胞癌中高表达,与肿瘤新生血管密切相关。近年来针对VEGF、VEGFR及信号传导通路的靶向治疗倍受关注。本文对此作～综述。     

结肠癌VEGF、TGF—β1、bcl-2表达与细胞增殖和血管形成的关系

目的研究血管内皮生长因子（VEGF）、转化生长因子β1（TGF—β1）和bcl-2在结肠癌组织中的表达及其与细胞增殖和肿瘤血管形成的关系。方法采用免疫组化方法检测42例结肠癌患者手术切除后石蜡包埋标本中VEGF、TGF—β1、bcl-2的表达，并根据血管内皮计数判定微血管密度（MVD）。结果结肠癌组织中VEGF、TGF—β1与bcl-2表达主要见于细胞胞浆内，较正常结肠组织表达明显增高。VEGF，bcl-2阳性的结肠癌组织MVD值明显高于VEGF，bcl-2阴性组织中MVD值（P〈0．01）；TGF—β1阳性癌组织与TGF—β1阴性癌组织MVD值无明显差异性。结论结肠癌组织中VEGF、TGF-β1促进肿瘤细胞增殖和血管的形成，bcl-2抑制肿瘤细胞凋亡，VEGF和TGF—β1与bcl-2无明显相关性。     

miR-1470对人肝癌细胞增殖和凋亡的影响

目的 探讨miR-1470对人肝细胞癌增殖和凋亡的影响。 方法 采用实时荧光定量PCR（quantitative real-time PCR，qPCR）检测人正常肝细胞株（LO2）和人肝癌细胞株（HepG2、Hep3B、Huh7）中miR-1470的差异表达；采用慢病毒转染肝癌细胞株，过表达（HepG2细胞株，过表达组）或敲减miR-1470（Huh7细胞株，抑制组）后，qPCR检测各组细胞miR-1470的表达；CCK8法检测细胞增殖改变；流式细胞术检测细胞凋亡情况。结果 miR-1470在肝癌细胞系HepG2、Hep3B和Huh7中的表达水平高于正常肝细 胞系LO2，HepG2、Hep3B、Huh7三种细胞系相对正常细胞表达量分别为：2.304±0.366、2.851±0.508、 5.768±0.445（均P＜0.05）。CCK8实验证实，过表达miR-1470组OD值在72 h显著高于对照组（P＜0.05），而抑制组显著低于对照组（P＜0.05）。流式细胞分析结果显示过表达miR-1470抑制肝癌细胞的凋亡（P＜0.05）；而miR-1470抑制组对比对照组，凋亡细胞显著增多（P＜0.05）。结论 miR-1470促进肝癌细胞增殖，抑制肝癌细胞凋亡。     

姜黄素雷公藤内酯醇对前列腺癌细胞PC3及血管内皮生长因子影响的比较

目的研究姜黄素（curcumin,Cur）、雷公藤内酯醇（triptolide,TL）对非雄激素依赖性前列腺癌细胞株PC3细胞体外作用及其血管内皮生长因子（vascular endothelial growth factor,VEGF）表达的影响。方法分别用梯度浓度的Cur和TL作用于PC3细胞,MTT法检测细胞生长活性;流式细胞仪测定细胞周期及凋亡的变化;半定量RT-PCR法检测PC3细胞内VEGF mR-NA的表达;ELISA检测细胞上清液中分泌VEGF蛋白的浓度。结果Cur及TL都能呈剂量与时间依赖性显著抑制PC3细胞的生长,不同浓度组之间及不同作用时间组之间的差异均有统计学意义（P〈0.01）。Cur、TL诱导PC3细胞分别出现剂量依赖性G2/M、S期阻滞（P〈0.01）,且各浓度组凋亡细胞比例差异有统计学意义（P〈0.01）;PC3细胞内VEGF mRNA的表达和细胞上清液中分泌VEGF蛋白亦呈剂量依赖性降低。结论Cur、TL能显著抑制体外PC3细胞的生长,分别促进细胞周期阻滞于不同时期,增加凋亡,并且VEGF mRNA及蛋白的表达明显降低,两药抑制肿瘤和血管生长机制不同。     

姜黄素对雄激素非依赖性前列腺癌细胞PC-3及血管内皮生长因子的影响

目的:研究姜黄素对雄激素非依赖性前列腺癌细胞株PC-3细胞体外作用及其对血管内皮生长因子(VEGF)表达的影响,探讨其抗肿瘤的作用机制。方法:分别用0、6.25、12.5、25、50μmol/L浓度的姜黄素作用于PC-3细胞,12、24、36、48、72、96h后台盼蓝拒染法、四甲基偶氮唑蓝(MTT)法检测细胞生长活性;24h后流式细胞仪测定细胞周期及凋亡的变化,透射电镜观察细胞超微结构变化;半定量RT-PCR法检测PC-3细胞内VEGFmRNA的表达;ELISA检测细胞上清液中VEGF浓度。结果:姜黄素能显著抑制PC-3细胞的增殖,呈剂量与时间依赖性,不同浓度姜黄素组之间及不同时间组之间差异均有统计学意义(P<0.01)。不同浓度姜黄素诱导PC-3细胞出现剂量依赖性G2/M期阻滞(P<0.01),且各浓度组凋亡细胞比例均显著高于空白对照组(P<0.01),差异有统计学意义;姜黄素作用24h后PC-3细胞出现凋亡的形态学改变;PC-3细胞内VEGF mRNA的表达和细胞上清液中VEGF呈剂量依赖性降低。结论:姜黄素能显著抑制体外PC-3细胞的生长,并促进其G2/M期阻滞和凋亡,VEGFmRNA及蛋白的表达也明显降低,可能是其抑制肿瘤和血管生长的机制之一。     

类风湿关节炎中巨噬细胞移动抑制因子对内皮细胞功能及血管内皮生长因子的影响

目的探讨巨噬细胞移动抑制因子（MIF）对类风湿关节炎（RA）滑膜内皮血管生成的影响和作用机制。方法免疫组化检查MIF在RA滑膜组织中的表达;加入MIF或PBS溶液培养人微血管内皮细胞株（HMEC-1）,CCK8法观察细胞的生长差异,磷脂酰丝氨酸凋亡试剂盒（AnnexinV法）检测细胞凋亡,RT—QPCR检测细胞中MIF及VEGF的表达差异。结果MIF在5例RA组织中均阳性表达;加入MIF的细胞株增殖显著较加PBS溶液的快（F=216．93,P〈0．01）,细胞株的凋亡被MIF显著抑制（凋亡率从21．37％降为7．01％（t=13．88,P〈0．01）;处于分裂相的细胞数目较加入PBS的细胞株多（G2期＋S期细胞比例从37．89％升为54．05％,t=5．42,P〈0．01）,在加入MIF的细胞株中VEGF的表达4．62倍高于加入PBS的细胞株（t=7．34,P〈0．01）。结论MIF在RA滑膜组织中表达,并通过提高血管内皮细胞的VEGF而促进RA滑膜血管生成而发挥重要的生理作用。MIF或许是治疗RA进展的药物靶点,有望通过抑制RA患者中MIF的表达从而延缓疾病的进展,改善患者的生活质量。     

姜黄素对雄激素非依赖性前列腺癌细胞PC-3及血管内皮生长因子的影响

目的：研究姜黄素对雄激素非依赖性前列腺癌细胞株PC-3细胞体外作用及其对血管内皮生长因子（VEGF）表达的影响，探讨其抗肿瘤的作用机制。方法：分别用0、6．25、12．5、25、50μmol／L浓度的姜黄素作用于PC-3细胞，12、24、36、48、72、96h后台盼蓝拒染法、四甲基偶氮唑蓝（MTT）法检测细胞生长活性；24h后流式细胞仪测定细胞周期及凋亡的变化，透射电镜观察细胞超微结构变化；半定量RT-PCR法检测PC-3细胞内VEGF mRNA的表达；ELISA检测细胞上清液中VEGF浓度。结果：姜黄素能显著抑制PC-3细胞的增殖，呈剂量与时间依赖性，不同浓度姜黄素组之间及不同时间组之间差异均有统计学意义（P〈0．01）。不同浓度姜黄素诱导PC-3细胞出现剂量依赖性G2／M期阻滞（P〈0．01），且各浓度组凋亡细胞比例均显著高于空白对照组（P〈0．01），差异有统计学意义；姜黄素作用24h后PC-3细胞出现凋亡的形态学改变；PC-3细胞内VEGF mRNA的表达和细胞上清液中VEGF呈剂量依赖性降低。结论：姜黄素能显著抑制体外PC-3细胞的生长，并促进其G2／M期阻滞和凋亡，VEGF mRNA及蛋白的表达也明显降低，可能是其抑制肿瘤和血管生长的机制之一。     

血管内皮生长因子受体-2在膀胱癌组织中的表达及其重要意义

血管内皮细胞生长因子（VEGF）在维持肿瘤微脉管系统中发挥了重要作用，针对其进行抗新生血管的治疗已成为肿瘤治疗的新靶点。VEGF受体（VEGFR）特别是VEGFR2，在上皮性肿瘤细胞中的表达异常，使VEGF以自分泌或旁分泌方式刺激肿瘤细胞生长并发生转移。     

caveolin-1抑制乳腺癌细胞体内外增殖及其机制探讨

目的研究caveolin-1对乳腺癌细胞MCF7在体内、体外生长和增殖的影响并初步探讨其机制。方法选用人类乳腺癌细胞MCF7,通过基因转染技术培育过表达caveolin-1的细胞株MCF7/cav-1作为实验组,空载体细胞株MCF7/vec作为对照组。Western blot方法检测转染细胞内caveolin-1和血管内皮生长因子（VEGF）的表达。软琼脂集落形成实验检测细胞增殖克隆的能力。建立裸鼠皮下种植瘤模型并检测肿瘤组织中Ki-67与VEGF的表达情况。结果 caveolin-1在MCF7/cav-1细胞中表达稳定,其表达量明显高于对照组细胞MCF7/vec（P〈0.01）和亲本细胞MCF7（P〈0.01）,而对照组细胞MCF7/vec和亲本细胞MCF7之间caveolin-1表达量差异无统计学意义（P〉0.05）。与MCF7/vec细胞比较,MCF7/cav-1细胞在软琼脂中形成的集落数目明显减少（P〈0.01）,体积也较小。MCF7/cav-1细胞中VEGF表达量明显低于MCF7/vec细胞（P〈0.01）。在裸鼠的体内实验中,与MCF7/vec细胞比较,MCF7/cav-1细胞在裸鼠体内生长缓慢（P〈0.01）,Ki-67染色明显减弱,VEGF染色阴性,提示caveolin-1可以抑制肿瘤体内增殖。结论 caveolin-1可能通过抑制VEGF表达抑制MCF7细胞生长和增殖。     

Autocrine and paracrine functions of vascular endothelial growth factor (VEGF) in renal tubular epithelial cells

BACKGROUND: VEGF secreted by organ parenchymal cells controls vascularization by recruiting endothelial cells and supporting their proliferation. In the developing kidney VEGF-expressing epithelial cells also express VEGF receptors. We showed that VEGF stimulates tubulogenesis in addition to promoting vascularization in metanephric explants. Since explants are grown in serum-free media and are not perfused, we hypothesized that VEGF secreted by renal epithelia may induce their proliferation in an autocrine manner and chemoattract endothelial cells. METHODS: To test these hypotheses, we analyzed VEGF-mediated responses in vitro using several renal epithelial cell lines [immortalized rat proximal tubular cells (IRPT), transformed mouse proximal tubular cells (tsMPT), and normal rat kidney cells (NRK-52E)] expressing VEGF receptors (VEGFR). RESULTS: We demonstrated that VEGFR-2 phosphorylates upon human recombinant VEGF (rhVEGF) exposure, indicating that VEGFR-2 is the signaling receptor. All three cell lines secreted VEGF into the media as indicated by enzyme-linked immunosorbent assay (ELISA) and Western blotting. We showed that these tubular epithelial cells chemoattract endothelial cells when cocultured in vitro and that the chemoattraction is abolished by anti-VEGF neutralizing antibody. rhVEGF (10 ng/mL) induced a mitogenic effect similar to 10% fetal bovine serum (FBS) as assessed by H(3)-thymidine incorporation and elicited 30% decrease in apoptosis as determined by annexin V-fluorescein isothiocyanate (FITC) staining. CONCLUSION: These in vitro studies indicate that (1) tubular epithelial cells chemoattract endothelial cells in a paracrine fashion by secreting VEGF, and (2) VEGF stimulates proliferation and promotes survival of renal epithelial cells in an autocrine manner via VEGFR-2. Taken together, our results suggest that VEGF supports the growth of renal epithelia in addition to mediating kidney vascularization.     

Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer

PURPOSE: Vascular endothelial growth factor has a critical role in maintaining tumor microvasculature and, as such, is an attractive target for anti-angiogenic therapy. Aberrant expression of VEGF receptors, especially VEGFR2, on epithelial tumor cells allows VEGF to stimulate growth and migration of tumor cells in an autocrine and/or paracrine manner. Therefore, we studied the expression of VEGF and VEGFR2 in bladder cancer, and the relationship to disease characteristics. MATERIALS AND METHODS: Expression of VEGF and VEGFR2 was studied in a cohort of 72 patients with transitional cell cancer of the bladder. Tumor tissues from all patients were analyzed by immunohistochemistry and examined by a pathologist blinded to patient outcome. Patient demographics and disease outcome were correlated with expression of these markers. Bladder cancer cell lines that express VEGFR2 were studied in vitro and in vivo to establish the significance of VEGF/VEGFR2 signaling. RESULTS: Expression of VEGF and VEGFR2 was observed in 58% and 50% of urothelial tumor cells, respectively. VEGF expression failed to correlate with clinical variables. However, VEGFR2 expression correlated with disease stage (coefficient 0.23, p = 0.05). In addition, VEGFR2 expression increased with tumor invasion into the muscle (p <0.01). Experiments with VEGFR2 positive bladder cancer cell lines in vitro demonstrated increased invasion in response to VEGF. In addition, VEGF inhibition augmented the effect of docetaxel in a murine xenograft model of bladder cancer with a significant inhibition in proliferative index and microvascular density, and induction of apoptosis. CONCLUSIONS: Increased VEGFR2 expression correlates with several features that predict progression of urothelial cancer, including disease stage and invasive phenotype. VEGF targeted therapy may enhance the efficacy of standard therapy for bladder cancer.     

Vascular endothelial growth factor stimulates embryonic urinary bladder development in organ culture

OBJECTIVES: To determine whether vascular endothelial growth factor A (VEGF) and its receptors are expressed during bladder development in mice when capillaries are forming, and whether exogenous VEGF might enhance the growth of endothelia and other types of bladder cells, using an embryonic organ-culture model. MATERIALS AND METHODS: Whole bladders from wild-type mice, at embryonic day (E) 14, were grown in serum-free organ culture in an air/5% CO2 atmosphere; some cultures were supplemented with VEGF and/or with VEGF receptor 1/Fc chimera (VEGFR1/Fc), which blocks VEGF bioactivity. Organs were harvested after 6 days and the expression of VEGF and related molecules assessed using immunohistochemistry. RESULTS: VEGF, VEGFR1 and VEGFR2 positive cells were immunodetected in E14 and E18 bladders. Exogenous VEGF increased whole-organ growth, as assessed by explant areas, total cell numbers, DNA and protein content; proliferation was enhanced, and apoptosis decreased, in urothelium and surrounding tissues. VEGF also increased the proportions of cells expressing endothelial (CD31) and smooth muscle (alpha smooth muscle actin) markers. VEGFR1/Fc blocked the growth-enhancing effects of exogenous VEGF. CONCLUSIONS: In organ culture, exogenous VEGF not only stimulated embryonic bladder endothelial cells but also strikingly enhanced the growth of the whole organ. Whether the effects of VEGF on diverse bladder cell populations are direct or indirect requires further investigation. The finding that VEGF protein is present in embryonic bladders in vivo raises the possibility that it has similar actions during normal development. The results also illuminate the pathobiology of certain bladder diseases in which VEGF levels have been shown to be increased.     

Glucose-regulated protein 78 silencing down-regulates vascular endothelial growth factor/vascular endothelial growth factor receptor 2 pathway to suppress human colon cancer tumor growth

Background

Up to 20% of colorectal cancer (CRC) is diagnosed with distant metastasis. The combination of chemotherapy with anti-vascular endothelial growth factor (VEGF) antibody can improve patient survival. Glucose-regulated protein 78 (GRP78) has an important role in cancer progression, but little is known about its role in VEGF production in CRC. The aim of this study was to explore the mechanism of GRP78 in two human colon cancer cell lines.

Methods

We first checked the expression of GRP78 in human normal and colon cancer tissues and two colon cancer cell lines. Glucose-regulated protein 78 was knocked down using GRP78 small interfering RNA (siRNA) in HT29 and DLD-1 cells. We examined knockdown cells by the cell growth kinetics in vitro and tumor growth rate in vivo, respectively. We also investigated the effect of GRP78 siRNA on the expression of hypoxia inducible factor (HIF-1α), VEGF, and VEGF receptor 2 (VEGFR2).

Results

Compared with their adjacent normal tissue, we detected high expression levels of GRP78 of surgically removed colon cancer tissues. Using GRP78 siRNA, we reduced the expression of GRP78 in HT29 and DLD-1 cells. The GRP78 knockdown cells had a lower proliferation rate with fewer colony-forming units in vitro and produced smaller tumors in vivo. In dissecting the mechanism underlying the reduced cell growth, we found that the down-regulation of GRP78 decreased the production of HIF-1α, VEGF, and VEGFR2 and suppressed angiogenesis.

Conclusions

Silencing GRP78 not only inhibits tumor, but also decreases the expression of VEGF and VEGFR2. Collectively, therapy targeting for GRP78 may inhibit the formation of colon cancer tumors via the HIF-1α/VEGF/VEGFR2 pathway.     

阿司匹林通过抑制STAT3磷酸化下调MCL-1和VEGF mRNA和蛋白表达促进胆囊癌细胞凋亡、抑制增殖

目的 探讨阿司匹林对人胆囊癌细胞株GBC-SD细胞凋亡及增殖的影响及其潜在机制。方法采用MTT法检测不同浓度梯度及作用时间下阿司匹林对GBC-SD细胞增殖的影响,流式细胞术检测阿司匹林对细胞凋亡的影响;Real-time PCR检测GBC-SD细胞中信号转导和转录激活因子3（STAT3）、髓细胞白血病因子-1（MCL-1）、血管内皮生长因子（VEGF）的mRNA表达水平,Western blotting检测STAT3、磷酸化信号转导与转录激活因子3（pSTAT3）、MCL-1、VEGF的蛋白表达情况。结果 阿司匹林对GBC-SD细胞增殖的抑制作用呈浓度依赖及时间依赖,与对照组相比差异有统计学意义（P＜0.05）。阿司匹林可促进GBC-SD细胞凋亡。阿司匹林可下调MCL-1和VEGF的mRNA表达水平,与对照组相比差异有统计学意义（P＜0.05）,但对STAT3 mRNA表达水平无明显影响（P＞0.05）。阿司匹林可下调pSTAT3、MCL-1、VEGF的蛋白表达水平（P＜0.05）,但对STAT3蛋白表达水平无明显影响（P＞0.05）;使用STAT3激动剂后,STAT3、pSTAT3、MCL-1、VEGF的蛋白表达水平高于未使用激动剂组（P＜0.05）,在激动剂组加入阿司匹林后,pSTAT3、MCL-1、VEGF的蛋白表达水平下调（P＜0.05）,但高于无激动剂组（P＜0.05）。结论 在GBC-SD细胞中,阿司匹林通过抑制STAT3磷酸化下调MCL-1、VEGF的mRNA及蛋白表达水平,从而促进胆囊癌细胞的凋亡,抑制增殖。     

Rab23基因的siRNA干扰诱导肝癌Huh7细胞凋亡

目的 观察信号通路Sonic bedgehog(Shh)抑制因子Rab23的RNA干扰对人肝癌细胞株Huh7增殖和凋亡的影响.方法 实验细胞分为转染组、隐性对照组和空白对照组.设计针对Rab23基因的siRNA,通过Liperfectemin 2000将其转染进Huh7细胞株,噻唑蓝(MTT)比色法试验检测沉默Rab23基因后第0、8、16、24和48 h的细胞数和MTr的D(λ)值;流式细胞术检测沉默Rab23基因48 h细胞凋亡情况.结果 转染组与空白对照组比较,加入siRNA后,8 h时细胞增殖数无明显减少,16、24和48 h时细胞数明显减少(P＜0.01),24、48 h时细胞存活率差异有统计学意义.隐性对照组与空白对照组比较差异无统计学意义(P＞0.05);Huh7细胞经siRNA作用48 h后,可见亚二倍体核型峰-凋亡峰.其中,转染组凋亡率为28%,隐性对照组及空白对照组未见凋亡峰.结论 Rab23对肝细胞癌的增殖起维持作用;通过沉默该基因可以抑制肝癌细胞增殖,并促进细胞凋亡.     

生长抑素抑制人结肠癌细胞增殖的实验研究

目的：研究外源性生长激素（GH）和生长抑素（SS）对人结肠癌细胞株HT-29的影响，并探讨其作用机制。方法：人结肠癌细胞株HT-29分成正常对照组、生长抑素组（SS组）、生长激素组（GH组）和生长抑素＋生长激素组（GH＋SS组）。MTT法测定细胞抑制率，流式细胞仪测定细胞周期分布、增殖指数、凋亡率，RT—PCR方法测定bcl．2及baxmRNA水平。结果：生长抑素能够明显抑制人结肠癌细胞株HT-29增殖（P〈0．01）、降低S期和G2／M期细胞比例（P〈0．05）、降低增殖指数（PI）（P〈0．05）、促进细胞凋亡（P〈0．01）、降低bcl-2mRNA表达（P〈0．05）、提高baxmRNA表达（P〈0．01），生长激素则无明显作用。GH＋SS组表现与SS组相似。结论：生长抑素可能通过抑制GdG．期细胞进入S期和G2／M期以及促进细胞凋亡两种途径抑制体外培养的人结肠癌细胞株HT-29增殖。生长抑素可能是通过改变bax基因和bcl-2基因的表达影响肿瘤细胞的凋亡。生长激素对体外培养的人结肠癌细胞株HT-29无显著影响。     

COX-2特异性抑制剂NS-398对胰腺癌生长及肿瘤血管 生成影响

目的:探讨COX-2特异性抑制剂NS-398对胰腺癌生长的影响及其机制。方法:分别用q RT-PCR与Western blot检测不同人胰腺癌细胞株(Bx PC-3、SWl990、Capan-2、Aspc-1、PANC-1)中COX-2及VEGF表达,并用MTT法检测NS-398在体外对人胰腺癌细胞增殖抑制作用;用体外实验最敏感细胞株建立裸鼠胰腺癌原位移植瘤模型,并随机将荷瘤鼠分为实验组和对照组,分别用NS-398与生理盐水处理,比较两组移植瘤的生长情况,并检测肿瘤组织中COX-2、VEGF蛋白表达及肿瘤微血管密度(MVD)。结果:各胰腺癌细胞中均有COX-2及VEGF表达,NS-398呈时间与浓度依赖性抑制各胰腺癌细胞的体外增殖,其中Bxpc-3细胞COX-2与VEGF表达量最高,且对NS-398最敏感。用Bxpc-3细胞建立原位移植瘤的实验组与对照组裸鼠比较,平均肿瘤体积明显减小(20.215 2 mm~3 vs.204.444 4 mm~3),瘤组织中COX-2与VEGF表达及MVD均明显降低(均P0.05)。结论:NS-398对胰腺癌的生长有抑制作用,其机制可能是通过COX-2途径降低VEGF基因表达从而抑制肿瘤血管生成有关。