选择性环氧合酶-2抑制剂联合奥曲肽诱导人胃癌细胞的凋亡

目的探讨选择性环氧合酶-2抑制剂NS-398与奥曲肽联合应用对人胃癌细胞株BGC-823生长、凋亡的影响。方法体外培养BGC-823细胞,分别用NS-398(100μmol/L)与奥曲肽(1μmol/L)单独及联合处理不同时间后,倒置显微镜观察细胞形态学变化;观察生长曲线的变化;流式细胞仪检测细胞凋亡率;实时定量(Real-time)PCR检测COX-2mRNA的表达;Western blot法检测Caspase-3蛋白表达。结果倒置显微镜下,对照组BGC-823细胞生长良好,药物处理后,细胞变小、变圆,悬浮,联合组细胞形态学改变显著强于单纯用药组;药物作用后,细胞生长受抑制,出现负增长,联合组作用明显强于单纯用药组;流式细胞仪检测表明联合用药组诱导BGC-823细胞的凋亡率明显高于单一用药组和对照组(P0.01);各处理组均使BGC-823细胞COX-2mRNA表达下调(P0.05);药物处理后细胞Caspase-3蛋白表达明显增加。结论 NS-398、奥曲肽联合可协同抑制BGC-823细胞生长、增殖,其机制可能与下调COX-2mRNA表达、诱导肿瘤细胞凋亡相关。     

5-Aza-CdR对人胃癌细胞株生物学行为及RASSFlA mRNA表达的影响

观察不同浓度的5-氮-2′-脱氧胞苷(5-Aza-CdR)对人胃癌细胞株BGC-823、SGC-7901、MKN-28生长及RASSF1A mRNA表达的影响。方法:分别以0．4μmol/L、1．6μmol/L、6．4μmol/L、25．6μmol/L、102．4μmol/L浓度的5-Aza-CdR处理人胃癌细胞株BGC-823、SGC-7901、MKN-28,MTT比色法测定72h时间段的吸光度值、计算抑制率,流式细胞仪检测5-Aza-CdR对胃癌细胞株生长周期及凋亡的影响,RT-PCR检测5-Aza-CdR处理前、后抑癌基因RASSF1A mRNA的表达。结果:5-Aza-CdR抑制体外培养人胃癌细胞株BGC-823、SGC-7901、MKN-28生长,呈浓度依赖性;5-Aza-CdR能有效诱导BGC-823、SGC-7901、MKN-28细胞凋亡;RT-PCR检测人胃癌细胞株SGC-7901、MKN-28无RASSF1A mRNA表达,经5-Aza-CdR处理后基因重新表达, BGC-823处理前后RASSF1A mRNA均有表达。结论:新型抑癌基因RASSF1A与胃癌的发生相关,5-Aza-CdR能抑制胃癌细胞株的增殖,并促进凋亡,其机制可能与RASSF1A基因的重新表达有关。     

重楼活性单体pp-10通过抑制PI3K/Akt通路诱导人胃癌细胞BGC-823凋亡和自噬

目的:探讨重楼/七叶一枝花(Paris polyphylla)的醇提物单体pp-10诱导人胃癌BGC-823细胞凋亡和自噬及其分子机制。方法:采用MTT法和克隆形成抑制实验观察不同浓度的重楼单体pp-10对人胃癌BGC-823细胞的增殖抑制作用;Hoechst33342染色法检测pp-10作用于人胃癌BGC-823细胞后细胞核形态的改变;Annexin V-FITC/PI双染法检测细胞凋亡;Western blotting检测重楼单体pp-10对细胞凋亡和自噬相关蛋白Caspase-3、Caspase-9、(ADP-核糖)聚合酶(PARP)、Bax、Bcl-2、LC3、P62以及PI3K/Akt信号通路相关蛋白(Akt、p-Akt、m TOR、p-m TOR、P70s6k、p-P70s6k)表达的影响。结果:重楼单体pp-10能显著抑制BGC-823细胞的生长,作用呈时间-效应关系及剂量-效应关系;克隆形成抑制实验表明随着pp-10浓度的增加,细胞克隆形成逐渐减少,与对照组相比有显著差异;在荧光显微镜下观察可见其细胞核固缩、边聚、裂解等细胞凋亡形态学变化;流式细胞术检测显示,随着作用药物浓度的增高,其凋亡率逐渐升高;Western blotting结果表明,随着药物浓度的增加,线粒体相关凋亡信号通路蛋白Caspase9、Caspase3及PARP均出现酶切活化条带,细胞促凋亡蛋白Bax的表达水平增加,抗凋亡蛋白Bcl-2减少,自噬相关蛋白Ⅱ型LC3增加,P62蛋白减少,p-Akt蛋白的表达水平下降,Akt下游蛋白p-m Tor、p-p70S6K表达减少。结论:重楼单体pp-10通过抑制BGC-823细胞增殖,诱导细胞凋亡和自噬,与下调P13K/Akt信号通路有关。     

CDX2基因高表达对胃癌细胞生物学行为的影响

目的探讨尾侧型同源转录因子-2(CDX2)基因过表达对胃癌BGC-823细胞增殖、迁移、凋亡等生物学特征的影响。方法采用脂质体转染法建立CDX2基因过表达的胃癌BGC-823稳定细胞株,分别采用RT-PCR、Western blotting和免疫细胞化学等方法检测转染重组表达载体pEGFP-C1/CDX2后,BGC-823细胞中CDX2基因及其蛋白的表达。MTT法检测CDX2基因过表达对细胞的增殖能力的影响;划痕实验检测CDX2过表达对细胞迁移能力的影响;流式细胞术检测CDX2过表达对细胞的凋亡的影响;应用基因芯片技术检测转染前后相关基因的差异表达。结果 RT-PCR及Western blotting检测结果显示,与对照组相比,转染pEGFP-C1/CDX2后,BGC-823细胞中CDX2基因和蛋白均呈高表达;CDX2过表达能明显降低转然组BGC-823细胞增殖能力和迁移能力;但对细胞凋亡影响不明显;基因芯片结果提示CDX2基因高表达能影响某些基因的表达。结论 CDX2过表达能明显抑制胃癌细胞增殖、降低迁移能力,提示CDX2在胃癌中可能发挥抑癌基因的作用。     

伊立替康联合去甲斑蝥素对人胃癌细胞作用的考察及协同作用机制研究

研究了伊立替康(CPT-11)联合去甲斑蝥素(NCTD)对人胃癌细胞BGC-823增殖的影响及协同作用机制.分别利用CPT-11 30、60、90、120、150μmol/L,NCTD 30、60、90、120、150μmol/L和两药按上述浓度1∶1联用,以及两药上述浓度完全交叉组合作用BGC-823细胞24、48和72 h,并且以不同序贯方式作用BGC-823细胞24 h.MTT法检测BGC-823细胞的增殖,采用中效原理评价两药联合作用;流式细胞术测定CPT-11 60μmol/L、NCTD 60μmol/L和联合用药(60∶60)μmol/L,以及不同序贯方式作用BGC-823细胞24 h后细胞周期及凋亡的情况;Western blot法检测CPT-11 30、60μmol/L,NCTD 30,60μmol/L和联合用药(30∶30,60∶60)μmol/L作用BGC-823细胞24 h后Pdcd4和p53蛋白表达水平.结果显示:CPT-11及NCTD联合用药比单独用药对细胞增殖的抑制作用增强,IC50明显减小(P0.05),单独使用CPT-11或NCTD作用24、48和72 h时的IC50分别是联合使用时的2.83、3.15、2.19倍以及2.66、3.11、2.45倍,并且两药联合用药具有协同作用效应;两药合用24 h时先给CPT-11方案抑制作用优于先给NCTD方案,且优于同时给药方案(P0.05);CPT-11 60μmol/L作用24 h引起BGC-823细胞S和G2-M期阻滞(P0.01),NCTD 60μmol/L作用24 h引起细胞G2-M期阻滞(P0.05),并诱导细胞凋亡(P0.05),联合用药(60∶60)μmol/L作用24 h,主要引起细胞G2-M期阻滞(P0.01),与先给NCTD 6h方案及同时给药相比,先给CPT-11 6h方案主要引起细胞S期阻滞增加(P0.05)以及细胞凋亡增加;CPT-11 30、60μmol/L作用12 h后Pdcd4上调表达,p53下调表达(P0.05),NCTD 30、60μmol/L作用12 h后Pdcd4下调表达,p53上调表达(P0.05),联合用药(30∶30,60∶60)μmol/L作用24 h后Pdcd4及p53蛋白表达均上调(P0.05).上述结果表明:CPT-11联合NCTD对人胃癌BGC-823细胞有协同抑制作用,其机制主要是诱导细胞G2-M期阻滞,并与抑癌基因蛋白Pdcd4及p53上调表达有关;两种药物联用时序贯次序对联合作用有影响,先给CPT-11方案要优于先给NCTD方案及同时给药方案,其机制主要是引起S期阻滞增加以及细胞凋亡增加;抑癌基因蛋白Pdcd4与p53之间可能存在负调控关系.     

白介素24与肿瘤

IL-24的抑癌机制复杂,可通过调节p38MAPK、PKR、β-通路;干扰线粒体功能和增加ROS合成;抑制DNA的修复、β-联蛋白(β-catenin)、P13K、ERK1／2和JNK1／2信号瘤血管形成和肿瘤细胞侵袭转移的能力等途径抑制肿瘤细胞的生长,促进凋亡。用复制缺陷的腺病毒携带的IL-24(AdlL-24)现已进入Ⅰ、Ⅱ期临床实验．与三氧化二砷、放疗联合应用可增加疗效。     

PKCα 由线粒体向细胞核转运与胃癌细胞凋亡诱导密切相关

PKC在细胞生长、分化、凋亡和信号转导调节中具有重要作用.通过激光扫描共聚焦显微镜证实:在胃癌BGC-823细胞中,一部分PKCα 定位于线粒体,一部分定位在胞浆,细胞经TPA处理后,位于线粒体和胞浆的PKCα 向细胞核转运;Western blot检测则发现PKCα 蛋白表达水平在TPA处理前后没有发生变化.此外,应用凋亡诱导剂和特异性PKC抑制剂的实验结果进一步证实:胃癌细胞内PKCα由线粒体和胞浆向细胞核转运与细胞凋亡的诱导密切相关.提示PKCα在细胞内的定向转运可能是与细胞凋亡过程相关联的重要事件之一.     

去甲斑蝥素对H446 细胞Id1mRNA 表达的影响

目的:观察去甲斑蝥素对小细胞肺癌H446细胞Id1mRNA表达的影响。方法:分别利用MTT法检测细胞生长活性;用划痕实验分析细胞迁移能力;采用Hoechst染色观察细胞凋亡;用实时荧光RT-PCR法测定H446中Id1mRNA的表达。结果:去甲斑蝥素对H446细胞的生长有明显的抑制作用,细胞的生长抑制率和凋亡率明显增加,细胞迁移距离明显缩短。去甲斑蝥素可抑制细胞内Id1mRNA的表达,其相对定量随去甲斑蝥素的浓度增大而减少。结论:在H446细胞中,去甲斑蝥素能抑制Id1mRNA的表达,这可能是去甲斑蝥素抑制细胞生长,迁移和诱导细胞凋亡的重要机制之一。     

大黄素抑制胃癌细胞糖酵解并促进凋亡

目的:探讨大黄素对人胃癌BGC-823细胞凋亡及糖酵解的影响。方法:采用不同浓度大黄素(30μmol/L、90μmol/L、180μmol/L)、磷脂酰肌醇3-激酶(Phosphatidylinositol 3 kinase,PI3K)抑制剂处理人胃癌BGC-823细胞,通过四甲基偶氮唑盐(MTT)检测细胞活力,采用试剂盒检测细胞葡萄糖消耗及乳酸水平,western blotting检测细胞己糖激酶Ⅱ、Bcl-2相关蛋白(Bcl-2 Associated X Protein,Bax)、PI3K、人低氧诱导因子1α(Human Hypoxia-inducible factor 1α,HIF-α)的表达。结果:大黄素能浓度依赖性的抑制BGC-823细胞增殖、葡萄糖消耗,降低乳酸水平;并降低己糖激酶Ⅱ的表达,促进凋亡蛋白Bax表达。PI3K抑制剂可抑制胃癌细胞糖酵解水平,而将大黄素与PI3K抑制剂联合使用后,与单一抑制剂组比,对细胞糖酵解抑制水平进一步加强,大黄素可下调PI3K下游蛋白及HIF-α的表达。结论:大黄素对人胃癌BGC-823细胞的增殖抑制作用其作用机制与调节PI3K途径及HIF-α,并抑制己糖激酶Ⅱ表达降低胃癌细胞糖酵解水平相关。     

靶向survivin的siRNA对胃癌BGC-823细胞增殖的影响

目的探讨干扰RNA沉默生存素（survivin）基因表达对人胃癌BGC-823细胞增殖和凋亡的影响。方法设计并合成3条靶向survivin的小分子干扰RNA（siRNA）,构建表达性干扰RNA质粒（shRNA）——shRNA-survivin-1、shRNA-survivin-2和shRNA-survivin-3,分别转染胃癌BGC-823细胞,实时定量PCR检测干扰RNA沉默survivin mRNA表达效果,Westernblot观察对胃癌BGC-823细胞survivin蛋白质表达的抑制,MTT（四甲基偶氮唑盐）比色法分析检测细胞生长抑制率,流式细胞计数检测各组细胞周期和凋亡率,探讨干扰RNA对胃癌BGC-823细胞生长的影响。结果在体外,shRNA-survivin-1有效沉默人胃癌BGC-823细胞survivin mRNA的表达,使sur-vivin mRNA相对水平明显降低（P〈0.05）,survivin蛋白质表达抑制,72h细胞生长抑制率达74.92%（P〈0.05）,shRNA-survivin-1使G2/M期细胞百分比明显增加,凋亡率显著增加（P〈0.05）。结论 shRNA-survivin-1可以沉默survivin基因的表达,可以显著抑制胃癌BGC-823细胞的增殖,在一定程度上诱导其自发凋亡。本研究为靶向sur-vivin的RNA干扰在胃癌的基因治疗提供了有力的理论依据和技术储备。     

Inhibition of two gastric cancer cell lines induced by fucoxanthin involves downregulation of Mcl-1 and STAT3

Fucoxanthin is a natural carotenoid that had never been previously demonstrated to have anti-tumor effect on human gastric adenocarcinoma SGC-7901 or BGC-823 cells. Here it was found to inhibit proliferation and induce apoptosis through JAK/STAT signal pathway in these cells; the mechanism by which this occurred was investigated. We find that fucoxanthin significantly increased the number of apoptotic cells by propidium iodide (PI) dye staining and flow cytometry. Fucoxanthin (50 or 75 μM) induced SGC-7901 cells cycle arrest at S phase, while BGC-823 cells arrest at G2/M phase. RT-PCR and western blot analysis revealed that the expressions of Mcl-1, STAT3 and p-STAT3 were obviously decreased by fucoxanthin in a dose-dependent manner. Synthetic siRNA targeting Mcl-1 was transfected into cells which had no effect on expressions of STAT3. After pretreatment with AG490 (50 μM) which led to blocking of the JAK/STAT signal pathway, the reductive expressions of Mcl-1, STAT3 and p-STAT3 caused by fucoxanthin were inhibited. This is the first analysis of effects on SGC-7901 and BGC-823 cells by fucoxanthin. Fucoxanthin can induce cell-cycle arrest and apoptosis in these cells. These effects involved downregulation of Mcl-1, STAT3 and p-STAT3. This work is significant for better understanding of mechanisms leading to human gastric adenocarcinoma formation and informing exploitation of anti-tumor marine drug, and for providing Mcl-1 and STAT3 as potential therapeutic targets for gastric adenocarcinoma.     

大豆低聚糖对人胃癌细胞株BGC-823细胞的细胞凋亡和细胞周期的影响

目的通过观察大豆低聚糖对胃癌癌细胞株BGC-823细胞的细胞周期和细胞凋亡的影响,探索乳酸杆菌发酵滤液对胃癌细胞作用的可能机制。方法用光镜和流式细胞仪分析不同浓度大豆低聚糖对BGC-823细胞的凋亡诱导效果;用流式细胞仪分析不同浓度大豆低聚糖对BGC-823细胞细胞周期的影响。结果大豆低聚糖可以诱导BGC-823细胞的凋亡。形态学观察处理后的BGC-823细胞,可见细胞变形,细胞皱缩,体积变小,细胞间隙增大,细胞核固缩。流式细胞仪分析50 mg/ml和100 mg/ml大豆低聚糖作用48 h和72 h BGC-823细胞的凋亡比例,分别为6.76%和7.93%。50 mg/ml大豆低聚糖作用48 h,引起BGC-823细胞G1期阻滞,100 mg/ml大豆低聚糖作用48 h,引起BGC-823细胞出现S期阻滞。结论大豆低聚糖可诱导部分BGC-823细胞凋亡。大豆低聚糖对BGC-823细胞的生长抑制作用在低浓度时可能通过G1期阻滞实现,在高浓度时可能通过S期阻滞实现。     

Stress Granules Inhibit Apoptosis by Reducing Reactive Oxygen Species Production

Cells can undergo two alternative fates following exposure to environmental stress: they either induce apoptosis or inhibit apoptosis and then repair the stress-induced alterations. These processes minimize cell loss and prevent the survival of cells with aberrant DNA and protein alterations. These two alternative fates are partly controlled by stress granules (SGs). While arsenite, hypoxia, and heat shock induce the formation of SGs that inhibit apoptosis, X-ray irradiation and genotoxic drugs do not induce SGs, and they are more prone to trigger apoptosis. However, it is unclear precisely how SGs control apoptosis. This study found that SGs suppress the elevation of reactive oxygen species (ROS), and this suppression is essential for inhibiting ROS-dependent apoptosis. This antioxidant activity of SGs is controlled by two SG components, GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and ubiquitin-specific protease 10 (USP10). G3BP1 elevates the steady-state ROS level by inhibiting the antioxidant activity of USP10. However, following exposure to arsenite, G3BP1 and USP10 induce the formation of SGs, which uncovers the antioxidant activity of USP10. We also found that the antioxidant activity of USP10 requires the protein kinase activity of ataxia telangiectasia mutated (ATM). This work reveals that SGs are critical redox regulators that control cell fate under stress conditions.     

Tetrandrine Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer BGC-823 Cells

Tetrandrine, a bis-benzylisoquinoline alkaloid isolated from the dried root of Hang-Fang-Chi ( Stephania tetrandra S. Moore), has been reported to possess anti-cancer effects on many tumors. In this study, we investigated tetrandrine-induced apoptosis on human gastric cancer BGC-823 cells in vitro and in vivo. The results showed that tetrandrine significantly inhibited cell viability in a dose- and time-dependent manner and induced apoptosis. It increased the apoptosis; upregulation of Bax, Bak, and Bad; and downregulation of Bcl-2 and Bcl-xl in BGC-823 cells. Moreover, tetrandrine increased the activation of caspase-3 and -9, release of cytochrome c, and upregulation of apaf-1, suggesting that tetrandrine-induced apoptosis was related to the mitochondrial pathway. Meanwhile, pretreatment with the pan-caspase inhibitor z-VAD-fmk in BGC-823 cells reduced tetrandrine-induced apoptosis by blocking activation of caspases. Furthermore, tetrandrine effectively inhibited tumor growth via apoptosis induction, which was verified by immunohistochemical analysis in a nude mouse xenograft model. Taken together, we concluded that tetrandrine significantly inhibited the proliferation of gastric cancer BGC-823 cells through mitochondria-dependent apoptosis, which may play a promising role in gastric cancer therapy.     

HSP72 inhibits apoptosis-inducing factor release in ATP-depleted renal epithelial cells

Inhibition of the mitochondrial release and nuclear translocation of apoptosis-inducing factor (AIF) by heat stress protein (HSP)72 may ameliorate apoptosis in renal epithelial cells exposed to a metabolic inhibitor. To evaluate this hypothesis, cells were transiently exposed to 5 mM sodium cyanide in the absence of medium glucose, a maneuver known to induce apoptosis. ATP depletion for 1-2 h resulted in the progressive accumulation of mitochondrial AIF in the cytosol of samples obtained by selectively permeabilizing the plasma membrane with digitonin. During recovery from ATP depletion, time-dependent nuclear AIF accumulation (but not cytochrome c, an F₀F₁ ATP synthase subunit, or talin) was observed in isolated nuclei. Nuclear AIF accumulation was associated with peripheral chromatin condensation and DNA degradation. Prior heat stress (HS) significantly reduced AIF leakage into the cytosol, decreased nuclear accumulation of AIF, and inhibited DNA degradation. HS also increased the interaction between AIF and HSP72 detected by immunoprecipitation. In ATP depleted cells, selective overexpression of human HSP72 reduced the leakage of mitochondrial AIF in a dose-dependent manner (r = 0.997). This study suggests that mitochondrial membrane injury and subsequent AIF release contribute to nuclear injury and apoptosis in ATP-depleted renal cells. HSP72, an antiapoptotic protein, inhibits cell injury in part by preventing mitochondrial AIF release and perhaps by decreasing its nuclear accumulation. heat stress; adenovirus; metabolic inhibitors; heat stress protein 60; DNA degradation     

Daidzein Induced Apoptosis via Down-Regulation of Bcl-2/Bax and Triggering of the Mitochondrial Pathway in BGC-823 Cells

Daidzein belongs to the group of isoflavones, found in a wide variety of plant-derived foods, especially in soybeans and soy-based foods. In this study, the effect of daidzein on human gastric carcinoma cells (BGC-823) and its mechanism were investigated. MTT assay was applied in the detection of the inhibitory effects of daidzein on cell proliferation. Hoechst–propidium iodide staining and flow cytometry were used to examine the apoptosis as well as the mitochondrial transmembrane potential. Western blotting was performed to detect the expression of apoptosis-associated proteins: cleaved PARP, cleaved caspase-9, cleaved caspase-3, Bcl-2, and Bax. Daidzein significantly inhibited the growth and proliferation of human gastric carcinoma cells (BGC-823) in a concentration- and time-dependent manner. Furthermore, it was found that an insult of daidzein to BGC-823 cells caused them to die by disruption of mitochondrial transmembrane potential, demonstrated not only by staining dead cells for phosphatidylserine but also by the up-regulation (cleaved PARP, cleaved caspase-9, cleaved caspase-3, Bax) and down-regulation (Bcl-2) of proteins associated with apoptosis and survival; whereas, the pan-caspase inhibitor z-VAD-fmk could partially rescue cells against damage of daidzein. Taken together, the results of this study demonstrate that daidzein significantly induces apoptosis via a mitochondrial pathway. Specifically, daidzein induced a change in the Bax/Bcl-2 ratios and activation of caspases-3 and -9 and the cleavage of PARP. Therefore, daidzein has the potential for use as a therapeutic agent for the treatment of gastric carcinoma.     

红车轴草提取物对胃癌BGC-823细胞凋亡的影响

探讨红车轴草(TrifoliumpratenseL)提取物对胃癌细胞株BGC-823的抑制增殖效应及诱导凋亡作用.我们采用不同浓度(50、100、250、500、1000mg/L)红车轴草提取物处理BGC-823细胞,采用四甲基偶氮唑盐(MTT)法检测药物对细胞的抑制作用,倒置显微镜观察细胞的形态学改变;AO/EB染色,荧光显微镜观察细胞凋亡形态;采用DNALadder观察DNA的降解;应用流式细胞仪观察细胞凋亡过程中的细胞周期的变化和细胞凋亡.结果显示在红车轴草提取物的作用下,BGC-823细胞呈凋亡改变,DNA琼脂糖凝胶电泳呈典型的凋亡特征.细胞凋亡的同时,细胞周期阻滞于G2/M期.实验结果表明红车轴草提取物能抑制胃癌BGC-823细胞增殖,能诱导胃癌细胞凋亡.     

n5-氟尿嘧啶敏感与非敏感的人胃癌BGC-823细胞基因表达谱差异分析

利用化疗药物5-氟尿嘧啶(5-Fu)对胃癌细胞株进行筛选和诱导,建立具有耐药性的胃癌细胞株.与亲代细胞株对比生长特性及基因表达谱,初步探讨胃癌细胞的耐药机制.采用四唑盐比色法（MTT）测定5-Fu 对胃癌细胞株BGC-823的半数抑制浓度（IC50）;根据IC50设计5-Fu剂量,用大剂量的5-Fu逐渐递增间歇给药的方法,反复筛选,获得5株胃癌耐药细胞株.比较耐药细胞株和亲本细胞株的形态和生长特性,继而再用人类肿瘤基因芯片（human cancer arrays）比较测试亲本与耐药细胞株的基因表达谱差异;对其中189个上调基因和133个下调基因采用Gene Ontology中的BP（Biological Process）分析这些基因相关的功能,并用MAS2.0分析这些基因可能涉及的信号通路．结果提示,胃癌细胞株耐药（5-Fu）相关基因可能与转录因子信号转导、TNF受体介导的细胞凋亡和抗凋亡、细胞周期调节、细胞粘附及MAP激酶类的功能相关．对细胞周期、信号转导相关的6个基因采用定量PCR验证,结果与基因表达芯片结果一致．上述结果有利于进一步发现胃癌细胞的耐药基因和相关信号通路,探索抗胃癌治疗的耐药机制．