In vitro inhibition of angiogenesis by hydroalcoholic extract of oak (Quercus infectoria) acorn shell via suppressing VEGF,MMP-2, and MMP-9 secretion

Context: Angiogenesis is an essential factor for cancer progression. Although more attention is paid in angiogenesis on its role in cancer biology, many other non-neoplastic diseases are also angiogenic-dependent. Recently, there is motivation to control cancer via inhibition of angiogenesis.

Objective: Quercus infectoria Olivier var (Fagaceae) (oak) is a plant whose different parts, such as its fruit shell, have been used extensively as a traditional drug in the west part of Iran. Although some biological properties of oak are determined, its effects on angiogenesis are unclear. So, we investigated the antiangiogenic effects of oak acorn shell.

Materials and methods: Fresh oak acorns were collected, and after authentication; hydroalcoholic extract of acorn shells (5, 10, 20, 30, 40, 60, 80, and 100 μg/ml) was used for evaluation of its cytotoxicity, antiproliferative, and antiangiogenic effects in vitro. Also, effects of the extract on vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 secretion were assayed using enzyme-linked immunosorbent assay (ELISA) and gelatin zymography. Results: Treatment with hydroalcoholic extract in eight doses resulted in a significant decrease of endothelial cell proliferation and angiogenesis with an IC₅₀ value of ~20 μg/ml, without any toxic effect. At 40 μg/ml, the extract inhibited MMP-9 activity; however, a dose-dependent reduction (60–80 µg/ml) in MMP-2 activity was seen. VEGF secretion was decreased with increase in the concentration of the extract from 5 to 100 μg/ml.

Discussion and conclusion: This study indicated that hydroalcoholic extract of oak acorn shell acts as a potent antiangiogenic agent which exerts its inhibitory effect mainly through downregulation of essential mediators such as VEGF and MMPs.     

力达霉素通过下调VEGF表达抑制斑马鱼胚胎血管生成

本研究采用斑马鱼胚胎模型研究力达霉素在整体动物水平对血管生成的影响。力达霉素处理胚胎后, 利用形态学观察、血管染色法、转基因斑马鱼检测其对胚胎血管生成影响, 以荧光定量PCR和蛋白免疫印迹法检测VEGF基因的表达情况。结果显示: 力达霉素处理后, 胚胎出现心包水肿、血流速度减缓等症状; 血管生长率降低, 肠下静脉生成受到抑制。荧光定量PCR和蛋白免疫印迹检测表明, 力达霉素对胚胎的VEGF mRNA表达水平没有影响, 但VEGF蛋白的表达受到显著抑制。研究结果表明, 力达霉素可以下调VEGF蛋白表达, 从而抑制斑马鱼胚胎血管生成。     

Recent developments in the inhibition of angiogenesis: examples from studies on platelet factor-4 and the VEGF/VEGFR system

Inhibition of angiogenesis is an important strategy to block tumor growth and invasion. We discuss herein results from our ongoing investigations on platelet factor-4 (PF-4) and the VEGF/VEGFR system. Platelet factor-4 (PF-4) is an anti-angiogenic ELR-negative chemokine. PF-4 inhibits endothelial cell proliferation and migration, and angiogenesis in vitro and in vivo. We have studied the structure and anti-angiogenic activities of a C-terminal fragment of PF-4 named PF-4 CTF. This molecule retains anti-angiogenic activity, blocks the interaction of angiogenesis factors with their receptors and may also be improved by mutation or domain-swapping. It seems, therefore, to be a good candidate for further development. Furthermore, we have developed a cyclic vascular endothelial growth inhibitor (Cyclo VEGI) from the structure of VEGF-A. In aqueous solution, cyclo-VEGI adopts an alpha helix conformation. Cyclo-VEGI inhibits binding of iodinated VEGF(165) to endothelial cells and angiogenesis. Furthermore, cyclo-VEGI significantly blocks the growth of established intracranial glioma in nude and syngeneic mice and improves survival.     

Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity

Uncontrolled tumor cell proliferation and robust neovascularization are prominent features of aggressive ovarian cancers. Although great efforts in anti-ovarian cancer therapy have been made in the past 4 decades, the 5-year survival rates for ovarian cancer patients are still poor, and effective drugs to cure ovarian cancer patients are absent. In this study, we evaluated the anti-cancer effects of lycorine hydrochloride (LH), a novel anti-ovarian cancer agent, using the highly-invasive ovarian cancer cell line, Hey1B, as a model. Our data showed that LH effectively inhibited mitotic proliferation of Hey1B cells (half maximal inhibitory concentration = 1.2 μM) with very low toxicity, resulting in cell cycle arrest at the G2/M transition through enhanced expression of the cell cycle inhibitor p21 and marked down-regulation of cyclin D3 expression. Moreover, LH suppressed both the formation of capillary-like tubes by Hey1B cells cultured in vitro and the ovarian cancer cell-dominant neovascularization in vivo when administered to Hey1B-xenotransplanted mice. LH also suppressed the expression of several key angiogenic genes, including VE-cadherin, vascular endothelial growth factor, and Sema4D, and reduced Akt phosphorylation in Hey1B cells. These results suggest that LH selectively inhibits ovarian cancer cell proliferation and neovascularization and is a potential drug candidate for anti-ovarian cancer therapy.     

胃癌组织PTEN蛋白、VEGF表达和血管形成的关系

目的研究胃癌组织中PTEN蛋白、血管内皮生长因子（VEGF）表达和血管形成的关系。方法采用免疫组织化学S-P法检测20例正常胃黏膜及80例胃癌组织中PTEN、VEGF、微血管密度（MVD）的表达。结果20例正常胃黏膜组织PTEN全部阳性表达，胃癌组织PTEN阳性率为52．5％（40／80）、PTEN蛋白表达水平与组织分化程度、淋巴结转移及TNM分期密切相关（P〈0．05），VEGF在正常胃黏膜阳性率为10％（2／20），胃癌组织阳性率为53．8％（43／80），二者差异有显著性（P〈0．01），VEGF表达与淋巴结转移及TNM分期密切相关（P〈0．05），胃癌组织MVD显著高于正常胃黏膜MVD（P〈0．01），MVD与胃癌组织浸润深度、分化程度、淋巴结转移及TNM分期密切相关（P〈0．01），胃癌组织中VEGF表达与MVD呈显著正相关（P〈0．01），PTEN蛋白表达水平与VEGF表达呈显著负相关（P〈0．01），PTEN蛋白表达水平与MVD呈显著负相关（P〈0．01）。结论PTEN蛋白表达与胃癌的临床病理特征密切相关，胃癌PTEN基因失活可能通过增加VEGF的表达来促进血管形成，导致肿瘤恶性进展。     

血管内皮生长因子反义寡核苷核对前列腺癌细胞PC3生长特性的影响

目的探讨血管内皮生长因子(VEGF)反义寡核苷核对前列腺癌细胞PC3生长特性的影响。方法采用新型脂质体Oligofectamine携带VEGF反义寡核苷酸转染激素非依赖性前列腺癌细胞PC3,实验分为对照组、反义寡核苷核苷酸组和正义寡核苷酸组。Western Blot杂交的方法检测细胞VEGF蛋白的表达,四甲基偶氮唑蓝法(MTT)检测细胞增殖变化,流式细胞仪检测细胞凋亡情况。结果新型脂质体可以携带VEGF反义寡核苷酸转染前列腺癌细胞PC3,与对照组和正义寡核苷酸组比较,反义寡核苷酸组细胞VEGF蛋白的表达明显下降,增殖受到明显抑制,凋亡率增加。结论新型脂质体Oligofectamine可以携带VEGF反义寡核苷酸成功转染前列腺癌细胞PC3,抑制VEGF的表达,进而抑制肿瘤细胞的增殖,促进其凋亡。     

鼻内翻性乳头状瘤及其癌变中CD105和VEGF表达的研究

目的:通过研究鼻内翻性乳头状瘤(NIP)及其癌变中CD105和血管内皮生长因子(VEGF)的表达情况,探讨CD105和VEGF在NIP发生过程中的作用.方法:采用鼠抗人CD105和鼠抗人VEGF单克隆抗体,应用免疫组织化学技术检测31例NIP和12例鼻内翻性乳头状瘤癌变(NIP SCC)组织标本中的微血管密度(MVD)及VEGF的表达;并同时检测21例下鼻甲(IT)组织标本中的MVD及VEGF的表达作为对照研究.结果:(1)VEGF在IT、NIP、NSCC中的表达结果分别为(12.06±2.27)%、(42.99±11.45)%、(97.43±12.9)%,VEGF在NIP和NSCC中的表达,均显著高于下鼻甲组织,VEGF在NSCC的表达显著高于NIP,两两相比有显著性差异(P＜0.01).(2)CD105在IT、NIP、NSCC中的表达结果分别为2.08±0.37、6.43±1.93、26.4±8.23,CD105在NIP和NSCC中的表达,均显著高于下鼻甲组织,CD105在NSCC的表达显著高于NIP,两两相比有显著性差异(P＜0.01).(3)NIP中VEGF与CD105的表达呈显著正相关(r=0.604,P＜0.01).结论:CD105和VEGF在NIP中表达明显不同于在IT、NIP SCC中的表达且两者关系密切.因而可共同作为NIP中新生血管有价值的标记物,可以认为是与NIP生长、转移及预后有关的重要指标.     

重组人血管内皮抑制素联合顺铂对人骨肉瘤MG-63细胞VEGF基因表达、增殖及侵袭力的影响

目的 观察重组人血管内皮抑制素(rhEndo)联合顺铂对人骨肉瘤MG-63细胞VEGF基因表达、增殖及侵袭力的影响.方法 顺铂、rhEndo、rhEndo联合顺铂分别处理MG-63细胞,采用RT-PCR和Western blot检测细胞VEGF mRNA和蛋白表达量,CCK-8实验检测细胞增殖,流式细胞术检测细胞凋亡,Transwell小室体外迁移实验检测细胞侵袭和迁移能力.结果 rhEndo联合顺铂组对VEGF mRNA和蛋白表达量、细胞增殖、侵袭迁移的抑制作用以及对细胞凋亡的促进作用均显著高于rhEndo、顺铂单药组,差异有统计学意义(P＜0.05).结论 重组人血管内皮抑制素联合顺铂能够在抑制骨肉瘤MG-63细胞VEGF表达、细胞增殖和侵袭力、促进细胞凋亡方面发挥协同作用.     

Basic fibroblast growth factor blockade enhances lung cancer cell invasion by activating the AKT/MMP‐2/VEGF pathway

Basic fibroblast growth factor (bFGF) can stimulate cancer cell growth and invasion; however, the influence of bFGF blockade remains unclear. Therefore, we aimed to explore the effects of bFGF blockade on the growth and invasion in A549 (high bFGF expression) and H2122 (low bFGF expression) lung cancer cells. We found that the blocking of bFGF by a neutralizing monoclonal antibody suppressed the growth of A549 cells but not of H2122 cells, as well as strongly induced the invasiveness of A549 cancer cells. Furthermore, bFGF blockade activated the AKT pathway and enhanced the expression levels of matrix metalloproteinase (MMP)‐2 and vascular endothelial growth factor (VEGF) in A549 cells. These responses could be reversed by treatment with AKT inhibitor and siMMP‐2, thus indicating the involvement of the AKT/MMP‐2/VEGF‐positive feedback loop. Finally, we confirmed that the anti‐bFGF‐induced invasion of cancer cells could be rescued by inhibiting the AKT/MMP‐2/VEGF loop. Our results revealed that bFGF blockade suppresses cell growth but promotes cell invasion in lung cancer cells with high bFGF expression levels. Our data further reinforced the importance of the AKT/MMP‐2/VEGF loop in regulating anti‐bFGF‐induced tumour cell invasion and suggested the limitations of the bFGF‐targeting strategy in lung cancer treatment.     

吉非替尼通过抑制EGFR/Akt信号通路特异性抑制平滑肌细胞增殖

目的:探讨表皮生长因子受体 (epidermal growth factor receptor,EGFR)抑制剂吉非替尼对平滑肌细胞(smooth muscle cells, VSMC) 和内皮细胞 (ndothelial cells, EC) 增殖的影响,以及对EGFR和Akt蛋白表达及磷酸化的影响。方法:将大鼠VSMC及EC置于含0.01~10 μmol·L的吉非替尼的培养基中培养24~72 h,以MTT法测定细胞增殖的抑制率。Western blot检测EGFR及磷酸化EGFR(p-EGFR)、Akt及磷酸化Akt(p-Akt)蛋白水平。结果:MTT结果显示,吉非替尼抑制VSMC增殖呈时间和浓度依赖性,而吉非替尼对EC增殖的抑制作用明显低于紫杉醇;Western blot结果显示VSMC中EGFR(1.07±0.13)表达与EC(0.58±0.05)相比明显增多(P<0.01),而吉非替尼可明显抑制VSMC中EGFR及Akt蛋白的磷酸化。结论:类似紫于杉醇,吉非替尼可抑制VSMC增殖,而对EC的细胞毒性作用明显低于紫杉醇,其机制可能是通过抑制EGFR及Akt蛋白磷酸化来实现的。     

血管内皮生长因子C表达与宫颈鳞状细胞癌局部淋巴管血管生成和浸润转移及预后的关系

目的 探讨血管内皮生长因子C（VEGF-C）表达与宫颈鳞状细胞癌局部淋巴管血管生成、浸润转移及预后的关系.方法 采用免疫组织化学法检测28例正常宫颈上皮、36例宫颈上皮内瘤变和68例宫颈鳞状细胞癌组织VEGF-C表达,同时检测血管内皮生长因子受体3（VEGFR-3）标记的微淋巴管密度、Ki-67标记的增殖指数和CD34标记的微血管密度.结果 VEGF-C在正常宫颈上皮组、宫颈上皮内瘤变组和宫颈鳞状细胞癌组的阳性表达率分别为21.43%、61.11%和72.06%,从正常宫颈上皮组到宫颈上皮内瘤变组及宫颈鳞状细胞癌,VEGF-C表达明显升高（P＜0.01）.在宫颈上皮内瘤变组,VEGF-C表达与微血管密度明显正相关（r=0.199,P=0.048）,VEGF-C阳性表达者微血管密度明显高于VEGF-C阴性表达者（F=4.112,P=0.049）.在宫颈鳞状细胞癌组,VEGF-C表达与微淋巴管密度显著正相关（r=0.288,P=0.017）,VEGF-C阳性表达者微淋巴管密度显著高于VEGF-C阴性表达者（F=6.488,P=0.013）.VEGF-C在宫颈鳞状细胞癌组表达与增殖指数及微血管密度均无显著相关性（增殖指数：r=0.085,P=0.489 微血管密度：r=0.181,P=0.139）.VEGF-C在宫颈鳞状细胞癌组表达与盆腔淋巴结转移、脉管浸润及生存率密切相关（P＜0.05）,而与患者年龄、国际妇产科协会（FIGO）分期、组织学分级及间质浸润深度无关（P＞0.05）.VEGF-C阳性表达者盆腔淋巴结转移及脉管浸润的发生率分别明显高于VEGF-C阴性表达者（P＜0.05）,而VEGF-C阳性表达者生存率明显低于VEGF-C阴性表达者（Log rank检验,P=0.0357）.结论 宫颈鳞状细胞癌VEGF-C过度表达可能促进局部淋巴管生成及肿瘤转移,可能提示预后不良.     

肾上腺髓质素对肾肿瘤细胞 PI3 K／Akt／eNOS／VEGF信号通路的作用

目的：研究肾上腺髓质素（ADM）对肾肿瘤细胞磷脂酰肌醇-3激酶（PI3K）／蛋白激酶B（Akt）／内皮型一氧化氮合酶（ eNOS）／血管内皮生长因子（ VEGF）信号通路的影响。方法将肾肿瘤细胞分为对照组、ADM组、VEGF组,ADM＋VEGF受体抑制剂组,ADM＋ADM shRNA组,每组设置24 h、48 h、72 h 3个时间梯度,western-blot检测对照组和ADM组细胞总蛋白中PI3K、Akt、eNOS、VEGF表达;检测VEGF组,ADM＋VEGF受体抑制剂组和ADM＋ADM shRNA组细胞总蛋白中PI3K、Akt、eNOS的表达。结果 PI3K、Akt、eNOS、VEGF在ADM组各时间梯度组肾肿瘤细胞中表达明显高于其在对照组细胞的表达（ P ＜0．05）。 PI3K、Akt、eNOS在VEGF组和ADM＋VEGF受体抑制剂组各时间组肾肿瘤细胞中表达明显高于其在对照组细胞中表达（ P ＜0．05）。 PI3K、Akt 、eNOS在ADM＋ADM shRNA组各时间组肾肿瘤细胞中表达与其在对照组细胞中表达差异无统计学意义（ P ＞0．05）。结论 ADM可激活PI3K／Akt／eNOS／VEGF信号通路;VEGF 受体抑制剂不能阻断 ADM 激活 PI3K／Akt／eNOS 信号通路。 ADM 一方面通过VEGF发挥肾肿瘤血管生成作用,另一方面通过其受体激活PI3K／Akt／eNOS信号通路参与肾肿瘤血管生成作用。ADM可能成为抗血管治疗肾肿瘤新的靶点。     

HIF,hypoxia and the role of angiogenesis in non-small cell lung cancer

Importance of the field: The role of angiogenesis in the initiation and progression of NSCLC and the molecular alterations leading to the growth of tumor vasculature are areas of great interest and recent therapeutic success.

Areas covered in this review: VEGF and its receptors play critical roles in the development of tumor vasculature and can be targeted by agents such as bevacizumab in the treatment of NSCLC. Furthermore, tumor hypoxia and the expression of the hypoxia-inducible factor (HIF) family of proteins are also linked to poorer survival in these patients. Recent studies using genetically engineered mouse models expressing stabilized HIF validate the importance of HIF in the evolution of NSCLC and demonstrate genetically that HIF is involved in NSCLC.

What the reader will gain: An overview of the key pathways and mediators of tumor angiogenesis, their relevance to the pathogenesis of NSCLC, and an update on the current status of angiogenesis inhibitors in NSCLC.

Take home message: Angiogenesis is a key mediator of NSCLC progression. Several antiangiogenic strategies are in clinical use and under development. While candidate predictive biomarkers of response to antiangiogenic therapy exist, they await independent and prospective validation.     

CD44V6、VEGF与非小细胞肺癌的相关性研究

目的研究非小细胞癌中CD44v6、VEGF表达与临床生物学行业相关性。方法回顾分析60例非小细胞肺癌的切除标本,采用免疫组化法检测肺癌组织中VEGF和CD44v6的表达,并分析临床意义。结果在非小细胞肺癌中,CD44V6和VEGF表达之间存在着正相关关系（OR=0.352）。两者共阳性组中淋巴结转移率为75%（24/32）,明显高于阴性者16.7%（1/6）,差别有显著意义（P〈0.05）。结论非小细胞肺癌患者中CD44V6和VEGF蛋白表达呈正相关,联合检测VEGF和CD44v6的表达对于非小细胞肺癌淋巴血行转移和病理分期的评估有一定临床意义,可指导临床选择正确的综合治疗方案。     

氧化苦参碱对SGC-7901胃癌细胞增殖及对血管内皮生长因子表达的影响

目的研究中药苦参有效成分氧化苦参碱对SGC-7901胃癌细胞增殖及对血管内皮生长因子(VEGF)表达的影响。方法用质量浓度为0.5,1.0,2.0,4.0,8.0 g·L^-1的氧化苦参碱干预SGC-7901胃癌细胞分别为0.5,1.0,2.0,4.0,8.0 g·L^-1质量浓度实验组,无任何药物处理的SGC-7901胃癌细胞为对照组。用噻唑蓝(MTT)法检测各组SGC-7901胃癌细胞培养第1,2,3,4天的增殖情况。用1.0,2.0和4.0 g·L^-1氧化苦参碱处理SGC-7901细胞并培养48 h后,用实时荧光定量-聚合酶链式反应(RT-PCR)法检测各组VEGF mRNA的表达情况。用酶联免疫吸附(ELISA)法检测各组蛋白表达情况。结果细胞培养第4天,对照组和0.5,1.0,2.0,4.0,8.0 g·L^-1实验组的增殖抑制率分别为(4.15±3.93)%,(14.79±1.66)%,(31.65±2.07)%,(41.57±2.93)%,(64.37±4.13)%,(79.17±4.75)%,与对照组相比,各质量浓度实验组SGC-7901胃癌细胞增殖抑制率均显著升高(P<0.01)。实验组的增殖抑制率随着培养时间和药物浓度的增加而增加(P<0.05或P<0.01)。氧化苦参碱干预48 h后,对照组和1.0,2.0和4.0 g·L^-1实验组VEGF mRNA表达量分别为0.82±0.03,0.65±0.05,0.54±0.06,0.46±0.04,与对照组比较,实验组VEGF mRNA表达量明显降低,且随氧化苦参碱质量浓度的升高其VEGF mRNA表达量呈逐渐降低趋势,组间差异均有统计学意义(均P<0.01)。对照组和0.5,1.0,2.0,4.0,8.0 g·L^-1实验组上清液中VEGF蛋白表达量分别为(1326.52±139.57),(1305.69±119.88),(1235.59±102.36),(1083.33±89.65),(789.85±95.26),(426.59±83.16)pg·mL^-1,与对照组相比,2.0,4.0,8.0 g·L^-1实验组细胞上清中VEGF蛋白表达量随氧化苦参碱质量浓度的增加而逐渐降低(P<0.05)。结论氧化苦参碱可抑制SGC-7901胃癌细胞增殖,增殖抑制率与作用时间、药物浓度呈正比,同时氧化苦参碱具有抑制相关肿瘤血管生成因子表达的作用。     

人参总皂苷对PDGF-BB所致血管平滑肌细胞增殖周期的影响

目的研究人参总皂苷(totel ginsenosides,TG)对血小板源性生长因子BB型(PDGF-BB)所致血管平滑肌细胞(VSMC)增殖周期的影响并探讨其可能的机制。方法组织块贴壁法培养SD大鼠胸主动脉平滑肌细胞,MTT比色法观察TG(10、30、100mg·L-1)对PDGF-BB(25μg·L-1)所致的VSMC增殖的影响;流式细胞仪分析细胞增殖周期;Re-al-timeRT-PCR检测VSMC中内皮型一氧化氮合酶(eNOS)、周期蛋白依赖性蛋白激酶抑制因子P27(KIP1)、原癌基因c-fos、周期蛋白D1(CyclinD1)mRNA的表达。结果在正常细胞中加入TG100mg·L-1不影响细胞的吸光度值及G0/G1期、G2/M期、S期细胞比例(P>0.05);PDGF-BB可明显升高吸光度值(P<0.01),增加S期细胞比例而降低G0/G1期细胞比例(P<0.01),并明显增加c-fos、CyclinD1 mRNA的表达,下调eNOS和P27(KIP1)的表达(P<0.01)。TG低、中、高浓度均明显抑制PDGF-BB诱导的吸光度值升高(P<0.01),降低S期细胞比例而升高G0/G1期细胞比例,明显下调PDGF-BB所致的c-fos及CyclinD1 mRNA高表达(P<0.01),并使eNOS mRNA表达升高(P<0.05),但对P27(KIP1)的表达无明显影响(P>0.05)。结论 TG通过阻止VSMC由G0/G1期进入S期而抑制PDGF-BB所致的增殖,其作用机制可能与其提高eNOSmRNA表达、降低c-fos和CyclinD1 mRNA高表达有关。     

小细胞肺癌中RECK基因的表达及与VEGF和MVD的关系

目的 探讨RECK基因与血管内皮生长因子(VEGF)表达、微血管密度(MVD)在小细胞肺癌(SCLC)的表达和相关性,及其与临床病理特征的联系.方法 采用免疫组化SP法检测43例肺癌组织和10例癌旁正常肺组织中RECK和VEGF、MVD的表达水平.结果 SCLC癌组织中RECK蛋白表达低于癌旁正常组织(P值为0.003),VEGF蛋白表达和MVD值高于癌旁正常组织(P值分别为0.011和0.001).三个指标在临床病理特征分析中数据差异未见统计学意义.RECK与VEGF表达无相关,RECK与MVD呈现负相关,且当VEGF表达高时两者负相关更加显著.结论 RECK基因与SCLC的侵袭和转移可能有一定关系.RECK、VEGF、MVD与患者的临床病理特征未见明显相关性.     

Ginsenoside Rg3 alleviates the migration,invasion, and angiogenesis of lung cancer cells by inhibiting the expressions of cyclooxygenase-2 and vascular endothelial growth factor

Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 μg/ml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial–mesenchymal transition (EMT)-related proteins, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit-8 (CCK-8), scratch, transwell, tube formation, and western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose-dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N-cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E-cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT-related protein expression levels in LC cells; however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF.     

水蛭素调节断指再植大鼠皮瓣成活、血管生成、炎症因子表达的作用

目的 探讨水蛭素调节断指再植大鼠皮瓣成活、血管生成、炎症因子表达的作用。方法 选取80只Wistar大鼠为研究对象,建立断指再植模型后随机分为两组：模型组、水蛭素组,均40只。水蛭素组大鼠皮瓣局部sc天然水蛭素6 ATU/次,2次/d,模型组大鼠sc生理盐水。术后7 d,观察大鼠皮瓣存活率;制备皮瓣组织匀浆,提取总蛋白,采用ELISA双抗体夹心法测定血管内皮生长因子（VEGF）、白细胞介素-6（IL-6）、细胞间黏附分子-1（ICAM-1）、肿瘤坏死因子-α（TNF-α）表达情况;采用免疫印迹法测定皮瓣中细胞外调节蛋白激酶（ERK1/2）、Bcl-2、p38丝裂原活化蛋白激酶（p38 MAPK）表达;HE染色法测定皮瓣中炎症介质浸润情况;CD34免疫组织化学染色法检测血管密度值。结果 水蛭素组大鼠皮瓣存活率、血管密度值、VEGF水平、ERK1/2相对表达量均明显高于模型组,而p38 MAPK、Bcl-2相对表达量,IL-6、ICAM-1、TNF-α水平明显低于模型组,差异均具有统计学意义（P < 0.05）。结论 水蛭素在断指再植模型大鼠中具有提高皮瓣成活率、促进VEGF表达、抑制细胞凋亡、减少炎症因子表达作用。