Claudin-23在胰腺癌细胞解离中的表达和定位变化

目的:探讨claudin-23表达和定位变化与胰腺癌细胞解离的关系。方法:利用RT-PCR、Western blot及免疫细胞化学方法观察胰腺癌细胞解离过程中claudin-23 mRNA和蛋白表达及其定位变化。结果:claudin-23 mRNA及蛋白在解离型高转移株胰腺癌细胞PC-1.0中低表达,而在非解离型低转移株胰腺癌细胞PC-1中高表达,表达MEK1-shRNA的PC-1.0亚细胞克隆中claudin-23 mRNA及蛋白表达增加,而在表达MEK2-shRNA的PC-1.0亚细胞克隆中表达变化不明显,但claudin-23蛋白定位发生明显变化。此外,表达MEK2-shRNA的PC-1.0亚细胞克隆呈岛样细胞克隆方式生长。与此相反,培养液上清中添加细胞解离因子后,claudin-23 mRNA和蛋白表达明显减少。结论:Claudin-23表达和定位变化与胰腺癌细胞解离状态密切相关,可能的分子机制为通过MEK信号转导通路调节claudin-23的表达和定位变化,从而调控胰腺癌的细胞解离。     

紧密连接蛋白claudin-1 及ZO-1 在胰腺癌中的表达*

目的:探讨紧密连接蛋白claudin- 1 及ZO- 1 在胰腺癌中的表达及在胰腺癌侵袭转移中的意义。方法:应用免疫组织化学方法检测claudin- 1 和ZO- 1 在胰腺癌不同侵袭位点（与非肿瘤胰腺组织相交界的胰腺癌侵袭前沿区、肿瘤中央区、与周围间质相交界的胰腺癌侵袭前沿区）及淋巴结转移灶和正常胰腺组织中的表达。结果:claudin- 1 与ZO- 1 蛋白正常定位于胰腺腺泡细胞和导管上皮细胞胞膜上,而在胰腺癌组织中,claudin- 1 与ZO- 1 蛋白定位从细胞膜异位至细胞浆或表达缺失,重度异位表达率分别为66.7% 和69.2% 。在与非肿瘤胰腺组织相交界处的胰腺癌组织中,低- 未分化胰腺癌的claudin- 1 重度异位表达率（91.7%）明显高于高- 中分化胰腺癌（55.6% ,P<0.05）;与周围间质相交界处的胰腺癌侵袭前沿区claudin- 1 重度异位表达率（89.7%）高于与非肿瘤胰腺组织相交界处的胰腺癌侵袭前沿区（66.7% ,P<0.05）;淋巴结转移灶重度异位表达率最高（92.3% ,P<0.05）。 同样与周围间质相交界处的胰腺癌侵袭前沿区ZO- 1 重度异位表达率（94.9%）也高于与非肿瘤胰腺组织相交界处的胰腺癌侵袭前沿区（64.2% ,P<0.05）,淋巴结转移灶最高（100% ,P<0.05）;原发胰腺癌组织各个位点中claudin- 1 与ZO- 1 表达呈正相关关系。结论:claudin- 1 和ZO- 1 异位表达对胰腺癌的发生起促进作用;claudin- 1 异位表达与胰腺癌的分化有关;claudin- 1 和ZO- 1 异位表达率增加促进胰腺癌的侵袭与转移。      

增强型绿色荧光蛋白基因稳定转染胰腺癌细胞

目的：建立稳定高表达增强型绿色荧光蛋白（EGFP）并能连续传代的胰腺癌细胞株。方法：将携带EGFP基因的pEGFP—C1质粒体外转染人胰腺癌细胞株SW1990，G418筛选稳定表达绿色荧光蛋白的细胞克隆并扩大培养，用荧光显微镜和流式细胞仪检测癌细胞荧光蛋白表达。结果：转染EGFP的胰腺癌细胞用G418筛选18天后，挑选克隆扩大培养，癌细胞几乎均见荧光蛋白表达并可连续稳定传至20代以上。结论：胰腺癌细胞株SW1990-EGFP的建立有助于构建理想的动物模型来研究肿瘤侵袭和转移的机制。     

PTEN、PIK3CA在培美曲塞耐药的胰腺癌细胞株Patu8988中的表达及其意义的初步探讨

目的 探索胰腺癌细胞株Patu8988对培美曲塞产生获得性耐药的机制,分析PTEN、PIK3CA在获得耐药前后mRNA及蛋白水平变化及其对细胞迁移及侵袭能力的影响。方法 通过RT-PCR及Western blot技术分别检测正常胰腺癌细胞株Patu8988及培美曲塞耐药的胰腺癌细胞株Patu8988中PTEN及PIK3CA的mRNA及其蛋白产物表达水平变化。应用迁移及侵袭实验分别检测正常胰腺癌细胞株和耐药的胰腺癌细胞株不同生物学行为。结果 RT-PCR发现与正常胰腺癌细胞株Patu8988相比,培美曲塞耐药的胰腺癌细胞株Patu8988中,PTEN和PIK3CA在mRNA水平表达均显著增高;Western blot发现培美曲塞耐药的胰腺癌细胞株Patu8988中PTEN、PIK3CA在蛋白水平同样表达升高,PTEN和PIK3CA在耐药的胰腺癌细胞株中的表达较正常胰腺癌细胞株分别上升89%和76%;迁移及侵袭实验的结果显示,培美曲塞耐药的胰腺癌细胞株Patu8988迁移及侵袭能力较正常胰腺癌细胞株Patu8988均显著下降(P＜0.05)。结论 PTEN、PIK3CA在对培美曲塞耐药的胰腺癌细胞株Patu8988中表达均异常升高,而同时高表达PTEN和PIK3CA的胰腺癌耐药细胞株的迁移及侵袭能力较正常胰腺癌细胞株显著降低,提示PTEN和PIK3CA共同参与胰腺癌细胞对培美曲塞产生获得性耐药过程,且有可能改变细胞的生物学行为。     

NK-1 R在胰腺癌中的表达、组织学定位和临床意义

目的 探讨胰腺癌中P物质（SP）受体NK－1R的表达、组织学定位，并将结果结合临床资料分析，以期找出其中相关性。方法 33个胰腺癌标本取自胰头癌根治术，男民生19例，女性14例，正常胰腺组织取自20个器官捐献者，男性11例，女性9例。应用实时定量逆转录聚合酶链反应（RQ－RT－PCR）技术，检测正常胰腺、胰腺癌组织和7株胰腺癌细胞中NK－1R的mRNA水平，应用Western blot技术检测NK－1R的蛋白水平，应用免疫组织化学方法进行NK－1R的组织学定位。结果 与正常胰腺相比，胰腺癌组织中NK－1R mRNA和蛋白都过度表达，免疫组织化学结果提示：正常胰腺的腺泡和导管中有微弱的NK－1R表达，胰腺癌组织中有较强的NK－1R表达，主要位于胰腺癌细胞、神经纤维和炎性细胞。结论 胰腺癌组织中NK－1R mRNA和蛋白表达水平都明显上调，扰乱了神经激肽的作用环节，促进胰腺癌细胞的发生和发展。     

nm23-H1基因表达与卵巢癌转移的相关性

背景与目的：转移是卵巢癌治疗失败及患者死亡的首要原因。然而,目前对卵巢癌转移潜能的分子机制知之不多。本研究旨在筛选高频转移卵巢恶性肿瘤细胞,分析卵巢癌高频转移细胞模型中nm23．H1基因表达与肿瘤转移特性的相关性,为系统实验研究和临床实践提供依据。方法：通过反复动物接种和体外培养,观察动物肺转移状况,筛选高频转移细胞株,比较原发肿瘤和转移肿瘤的特征,并应用Northem blot和Westem blot方法测定各类肿瘤细胞nm23 mRNA和蛋白表达水平。结果：8株卵巢恶性肿瘤细胞中,4株有较高转移潜能,多次培养接种可筛选出高频转移细胞亚群。各类细胞nm23mRNA和蛋白表达水平与肿瘤转移特性呈负相关(r=0．96,P=0．0001)。结论：由基因分子水平决定的肿瘤转移趋势在不同肿瘤种类及细胞亚群中有明显差异;卵巢癌中nm23 mRNA和蛋白的表达与其转移能力的降低有密切关系,可作为判定卵巢癌预后的敏感指标。     

脂氧合酶抑制剂NDGA对胰腺癌细胞PCNA-1增殖和凋亡的影响

目的：探讨脂氧合酶抑制剂NDGA对人胰腺癌细胞株PCNA-1生长抑制、诱导凋亡及其对bcl-2、bax表达的影响。方法：采用MTT法检测NDGA对胰腺癌细胞株PCNA-1增殖活性的影响,流式细胞术检测NDGA处理的胰腺癌细胞株PCNA-1的细胞周期及凋亡相关蛋白bcl-2、bax的表达。结果：NDGA抑制胰腺癌细胞株PCNA-1的增殖活性,呈剂量依赖效应关系;细胞经100μmol／L的NDGA处理后G0／G1期细胞减少（P〈0．05）、S期细胞增多（P〈0．05）,G2／M期细胞无明显变化;细胞经100μmol／L的NDGA处理48h后bcl-2蛋白与对照组相比表达下调（P〈0．01）、bax蛋白与对照组相比表达上调（P〈0．01）。结论：NDGA对胰腺癌细胞株PCNA-1有抑制增殖、诱导其凋亡作用,诱导细胞凋亡的机制可能与细胞凋亡相关基因bcl-2表达下调、bax表达上调有关。     

siRNA抑制人高迁移率族蛋白1表达对前列腺癌PC-3增殖的影响

目的：研究小干扰RNA（small interfering RNA，siRNA）抑制高迁移率族蛋白1（HMGB1）基因的表达对人前列腺癌细胞PC-3增殖的影响。方法：构建真核表达载体Pgenesil-1／HMGB1 siRNA，在脂质体Lipofectamina 2000的介导下转染前列腺癌PC-3细胞株，通过RT—PCR和Westerll Blot检测HMGB1的mRNA及蛋白质的变化；流式细胞仪检测细胞周期；噻唑蓝（MTT）检测细胞生长曲线观察转染后PC-3细胞HMGB1基因表达和体外增殖活性的变化。结果：成功构建siRNA表达载体Pgenesil-1／HMGB1 siRNA，所获表达载体转染可使PC-3细胞HMGB1 mRNA和蛋白表达水平显著降低（P〈0．05），并能有效抑制PC-3增殖活性（P〈0．05）。结论：应用siRNA干扰技术能有效的抑制HMGB1基因的表达，同时也可有效抑制癌细胞的体外增殖活性，为肿瘤的生物学治疗提供新思路。     

神经菌毛素在胰腺癌组织及MIA PaCa-Ⅱ细胞系中的表达

目的探讨神经菌毛素（Neuropilin-1，NRP-1）在胰腺导管癌组织及MIA PaCa-Ⅱ胰腺癌细胞系中的表达及意义。方法运用免疫组化和RT-PCR法分别检测在正常胰腺组织、癌旁组织、胰腺癌组织及MIA PaCa-Ⅱ细胞系中Neuropilin-1蛋白及mRNA表达水平。结果蛋白水平：可见正常胰腺组织无表达，癌旁组织轻度表达，而胰腺癌组织及MIA PaCa-Ⅱ胰腺癌细胞中高水平表达。神经组织也可表达Neuropilin-1 mRNA水平见正常胰腺组织呈微量表达，癌旁组织中度表达，而胰腺癌组织及MIA PaCa-Ⅱ胰腺癌细胞中呈高水平表达。结论Neuropilin-1可能与参与了胰腺癌的发生发展，在胰腺癌神经转移中可能起着重要作用。     

miR-449a对胰腺癌细胞放射敏感性影响

目的 研究miR-449a对胰腺癌SW1990细胞放射敏感性的影响方法 qRT-PCR检测放疗前后胰腺癌SW1990细胞系中miR-449a的表达变化,利用Lipofectamine 2000转染试剂盒将miR-449a mimics及miR-NC转染到SW1990细胞中,流式细胞术、克隆形成实验检测放射处理后细胞放射敏感性变化。使用TargetScan预测及双荧光素酶报告基因实验证明miR-449a与Cyclin D1的靶向作用,免疫组织化学法观察Cyclin D1在胰腺癌组织和胰腺癌旁5 cm的正常胰腺组织的分布,基因敲除Cyclin D1验证其对胰腺癌细胞放射敏感性的影响。结果 经放射处理后,miR-449a在胰腺癌细胞中的表达量明显降低;过表达miR-449a增加了放射后胰腺癌细胞的凋亡率,并使胰腺癌细胞克隆形成率也明显降低;TargetScan预测及双荧光素酶报告基因实验证实了Cyclin D1是miR-449a的靶标;Cyclin D1蛋白在胰腺癌患者组织中的阳性染色率(70%,35/50)明显高于正常胰腺组织(20%,2/10),Cyclin D1增加了胰腺癌细胞的放射敏感性。结论 miR-449a通过靶向干扰Cyclin D1的表达,促进胰腺癌细胞的放射敏感性。     

Involvement of the mitogen-activated protein kinase kinase 2 in the induction of cell dissociation in pancreatic cancer

In our previous investigation, mitogen-activated protein kinase kinase 2 (MEK2) was detected as a factor which was correlated to the potential of invasion-metastasis. In this study, the immunocytochemical, immunohistochemical and mRNA expressions of MEK2 were examined in pancreatic cancer cell lines and tissue samples, respectively. Constitutive expressions of MEK2 and phosphorylated MEK (p-MEK) were observed in PC-1.0 and ASPC-1 cells, which exhibited a growth pattern of single cells, whereas the relevant expressions were quite faint in PC-1 cells and CAPAN-2 cells, which exhibited a growth pattern of island-like clonies. Simultaneous inductions of MEK2 expressions and cell dissociation were observed after the treatment with a conditioned medium (CM) of PC-1.0 cells. The expression of MEK2 and p-MEK were reduced and the cell aggregation was found in PC-1.0 and ASPC-1 cells after U0126 (a MEK inhibitor) treatment. In vivo, both the MEK2 and p-MEK overexpressed in human pancreatic cancer tissues and p-MEK was found to be more strongly expressed in the invasive front than that in the center of tumor (P<0.05). MEK2 is closely related to pancreatic cancer cell dissociation. MEK2 activation is probably involved in the first step of the cascade in the invasion-metastasis of pancreatic cancer.     

Analysis of invasion-metastasis mechanism in pancreatic cancer: involvement of tight junction transmembrane protein occludin and MEK/ERK signal transduction pathway in cancer cell dissociation

Mitogen-activated protein kinase kinase 2 (MEK2) was detected as an invasion-metastasis related factor between highly invasive (PC-1.0) and weakly invasive (PC-1) pancreatic cancer cell lines in our previous study. On the other hand, tight junction (TJ) was found to be correlated with carcino-genesis and tumor development. In this study, the expressions and correlation of TJ transmembrane protein occludin and MEK/extracellular signal-regulated kinase (ERK) signaling pathway were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines were analyzed immunocytochemically with anti-occludin, phosphorylated MEK1/2 (p-MEK1/2), phosphorylated ERK1/2 (p-ERK1/2) antibodies. MEK1/2 inhibitor U0126 significantly induced the expression of occludin at the cell-cell junction and substantially suppressed the p-MEK1/2 and p-ERK1/2 expressions in PC-1.0 and AsPC-1 cells. In contrast, dissociation factor (DF) treatment obviously disrupted the occludin expressions at the sites of cell-cell junction and markedly induced the p-MEK1/2 and p-ERK1/2 expressions in PC-1 and CAPAN-2 cells. In addition, occludin expressions at cell-cell junction were restored and p-MEK1/2 and p-ERK1/2 expressions were suppressed by subsequent U0126-treatment in DF treated PC-1 and CAPAN-2 cells. Correspondingly, light microscopic images showed that DF induced the dissociation of cell island-like colonies in PC-1 and CAPAN-2 cells, and U0126-treatment induced cell aggregation in these pancreatic cancer cells. Occludin is involved in the cell dissociation in pancreatic cancer cells. Moreover, MEK/ERK signaling pathway probably regulates the cell dissociation status of pancreatic cancer through influencing the intracellular localization and expression of occludin.     

Arrangement of expression and distribution of tight junction protein claudin-1 in cell dissociation of pancreatic cancer cells

Mitogen-activated protein kinase kinase 2 (MEK2) was isolated previously as a potential factor related to cancer cell dissociation in highly (PC-1.0) and weakly (PC-1) invasive pancreatic cancer cells. On the other hand, changes of structure and function of tight junction (TJ) are reported to be correlated with carcinogenesis and tumor development. In this study, immunocytochemistry and Western blot analysis were performed in pancreatic cancer cells using anti-claudin-1, MEK2 and phosphorylated MEK1/2 (p-MEK1/2) antibodies to reveal the correlation between TJ and cancer cell dissociation, as well as the involvement of MEK2 in regulation of TJ in cell dissociation of pancreatic cancer. After incubation with conditioned medium of PC-1.0 cells, plasma membrane distribution of claudin-1 was obviously disrupted, and expressions of MEK2 and p-MEK1/2, as well as dissociation of cell colonies, were significantly induced in PC-1 and CAPAN-2 cells. However, U0126 (a MEK1/2 inhibitor) treatment apparently induced the plasma membrane distribution of claudin-1 and aggregation of single cells in PC-1.0 and AsPC-1 cells, synchronously seriously suppressed MEK2 and p-MEK1/2 expression. Arrangement of expression and distribution of claudin-1 is closely related to cell dissociation status in pancreatic cancer cells through MEK2 activation.     

Relationship between the expression of extracellular signal-regulated kinase 1/2 and the dissociation of pancreatic cancer cells: Involvement of ERK1/2 in the dissociation status of cancer cells

Mitogen-activated protein kinase kinase 2 (MEK2), the upstream kinase of extracellular signal-regulated kinase 1/2 (ERK1/2) was previously isolated as cancer cell dissociation related factor. In this study, to further clarify the regulatory mechanism of cancer cell dissociation, two hamster (PC-1.0 and PC-1) and human (Capan-2 and AsPC-1) pancreatic cancer cell lines were analyzed immunocytochemically with anti-ERK1, anti-ERK2 and anti-phosphorylated ERK1/2 (p-ERK1/2) antibodies. U0126 (a MEK1/2 inhibitor) significantly suppressed ERK2 and p-ERK1/2 expressions in PC-1.0 and AsPC-1 cells (P<0.05). Cancer cell dissociation factor (DF) markedly induced ERK2 and p-ERK1/2 expressions in PC-1 and Capan-2 cells (P<0.05), and the induced ERK2 and p-ERK1/2 expressions were inhibited by subsequent U0126-treatment (P<0.05). Simultaneously, light microscopic images showed that DF clearly induced cell dissociation in PC-1 and Capan-2 cells, while U0126-treatment induced cell aggregation in these pancreatic cancer cells. ERK2 activation is closely involved in cell dissociation of pancreatic cancer cells.     

Relationship between activation of epidermal growth factor receptor and cell dissociation in pancreatic cancer

In our previous investigations, mitogen-activated protein kinase kinase 2 (MEK2)/extracellular signal-regulated kinase 2 (ERK2) signaling pathway was found to be correlated with the cell dissociation induced by dissociation factor (DF) in pancreatic cancer cells. In this study, the expressions of epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and its downstream kinases MEK1/2 and ERK1/2, were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and two human (AsPC-1 and Capan-2) pancreatic cancer cell lines were used. Immunocytochemical study was performed using anti-EGFR, p-EGFR, phosphorylated MEK1/2 (p-MEK1/2), and phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF-treatment markedly induced the expressions of EGFR, p-EGFR, p-MEK1/2, p-ERK1/2, as well as the dissociation of cell colonies in PC-1 and Capan-2 cells. In contrast, AG1478 (an EGFR inhibitor) treatment significantly induced the cell aggregation in PC-1.0 and AsPC-1 cells which usually grew as single cells, but strongly suppressed the expressions of EGFR, p-EGFR, p-MEK1/2, and p-ERK1/2. These observations demonstrate that activation of EGFR is closely involved in cell dissociation in pancreatic cancer through activating MEK/ERK signaling pathway.     

AKRIC3基因沉默对前列腺癌PC3细胞转移潜能及多西紫杉醇敏感性影响研究

目的：探讨AKRlC3基因沉默对前列腺癌PC3细胞增殖与转移以及多西紫杉醇药物敏感性的影响。方法：通过脂质体转染的方法将GAPDH-pGIPZshRNA和AKRIC3-pGIPZshRNA瞬时转染前列腺癌PC3细胞。实验分为对照组、阴性对照组（GAPDH-pGIPZshRNA）和实验组（AKRlC3-pGIPZshRNA）。通过蛋白质印迹法检测转染72h后PC3细胞中AKRIC3蛋白的表达;细胞计数法检测各组前列腺癌PC3细胞的生长曲线及多西紫杉醇对各组细胞的抑制作用;划痕实验检测各组前列腺癌PC3细胞的迁移能力。结果：shRNA转染前列腺癌PC3细胞48h后荧光显微镜下细胞发绿色荧光。蛋白质印迹法结果表明,实验组AKRIC3蛋白表达下降,相对表达量为（5．71±0．03）％,明显低于阴性对照组（9．75±0．08）％和对照组（9．55±0．05）％,F=44．050,P〈0．001。同时PC3细胞生长速率变慢,对多西紫杉醇的药物敏感性增加,实验组耐药IC50（27．81±0．02）nmol／L明显低于对照组（60．26±0．03）nmol／L和阴性对照组（59．94±0．05）nmol／L,F-823200．711,P〈0．001。实验组细胞迁移能力下降。结论：前列腺癌PC3中AKRIC3基因的沉默能有效影响肿瘤细胞增殖、迁移和对多西紫杉醇药物的敏感性,提示AKRIC3有望成为前列腺癌治疗的靶基因。     

抑制survivin基因对人卵巢癌SKOV3细胞顺铂药物敏感性的影响

目的：探讨应用RNAi技术下调survivin基因对人卵巢癌SKOV3细胞增殖、凋亡及顺铂敏感性的影响。方法：构建survivin基因shRNA真核表达载体,转染人卵巢癌SKOV3细胞。定量PCR和Western blotting观察SKOV3细胞survivinmRNA和蛋白表达的改变;噻唑蓝（Myr）检测细胞增殖活性和药物敏感性;流式细胞仪检测细胞凋亡。结果：SKOV3-siRNA组细胞survivinmRNA及蛋白表达下降,同时细胞增殖能力明显降低,细胞凋亡率显著增加（P〈0．05）。SKOV3-siRNA组细胞对顺铂的化学敏感性升高,顺铂的IC50值降低（P〈0．05）。结论：下调survivin基因表达能够抑制卵巢癌SKOV3细胞增殖能力,诱导细胞凋亡,增强细胞顺铂药物敏感性。因此,survivin基因可能成为抗肿瘤治疗的潜在靶点。     

Midkine shRNA对胃癌SGC7901细胞增殖与凋亡的影响

目的：研究shRNA干扰midkine对胃肿瘤细胞SGC7901生物学特性的影响。方法：构建midkine基因的特异性小RNA干扰质粒,采用脂质体2000转染SGC7901细胞,检测细胞的增殖和克隆形成能力以及细胞凋亡情况。结果：与对照组相比,转染重质粒后1—5天,SGC7901细胞增殖明显受到抑制（P〈0．01）,细胞形成克隆数明显降低（P〈0．01）,并且有明显的亚二倍体峰出现（P〈0．05）。结论：针对midkine基因的特异性小RNA干扰质粒在体外能有效抑制人胃癌细胞SGC7901 midkine表达,细胞增殖及克隆形成能力减弱,细胞凋亡增加,为midkine基因靶向治疗提供一定的实验依据。     

法舒地尔对胃癌MGC-803细胞增殖、侵袭和迁移的影响

目的 探讨法舒地尔对胃癌MGC-803细胞增殖、侵袭和迁移的影响及可能机制。方法 采用不同浓度的法舒地尔处理胃癌MGC-803细胞,检测细胞数目;选择无显著细胞毒性的3组浓度（10、25、50 μmol／L）法舒地尔进行后续实验,将经药物处理的胃癌MGC-803细胞作为处理组,而未经药物处理的胃癌MGC-803 细胞作为对照组;细胞培养0、24、48、72、96 h后,CCK-8法检测细胞增殖倍数;划痕实验检测细胞迁移能力;Transwell法检测细胞侵袭能力;Western blotting检测细胞中血管内皮细胞生长因子（VEGF）、基质金属蛋白酶9（MMP-9）、基质金属蛋白酶14（MMP-14）和上皮间质转化（EMT）的标志蛋白波形蛋白（Vimentin）和上皮型钙黏蛋白（E-cadherin）的表达水平。结果 CCK-8法检测结果显示,法舒地尔以剂量依赖性的方式抑制胃癌MGC-803细胞的生长,法舒地尔浓度越高,处理组的细胞数量越少,增殖倍数明显降低（P＜0.01）;划痕实验结果表明,处理组伤痕愈合率明显较对照组降低,且法舒地尔浓度越高,处理组伤痕愈合率越低（P＜0.01）;Transwell结果显示,与对照组比较,处理组侵袭的细胞数目明显减少（P＜0.01）;与对照组比较,法舒地尔明显下调VEGF、MMP-9、MMP-14和Vimentin蛋白的表达水平,而上调E-cadherin蛋白的表达水平。结论 法舒地尔可抑制胃癌MGC-803细胞的的增殖、迁移和侵袭能力,降低MMP-9、MMP-14、VEGF表达水平,为胃癌的治疗研究提供新思路和理论基础。