miR-204在胃癌组织中的表达及对胃癌细胞凋亡的影响

目的探讨miR-204在胃癌组织中的表达与临床病理参数的关系及其对胃癌细胞凋亡的影响。方法接受手术治疗的胃癌患者53例,收集手术切除的胃癌组织作为胃癌组标本,并收集其癌旁(3 cm)正常组织作为对照组标本,同时培养人胃癌细胞株(BGC823、SGC7901)和永生化胃上皮细胞株(GES-1)。采用逆转录-聚合酶链反应(RT-PCR)检测胃癌组标本、对照组标本、BGC823、SGC7901、GES-1细胞株中的miR-204表达,分析胃癌组组织miR-204相对表达量与临床病理参数的关系,对部分BGC823、SGC7901细胞株进行转染miR-204,对比转染miR-204组与未转染miR-204组的BGC823、SGC7901细胞株的细胞增殖和细胞凋亡情况。结果胃癌组标本中的miR-204相对表达量明显低于对照组标本中miR-204的相对表达量(P0.05)。BGC823细胞株和SGC7901细胞株中的miR-204相对表达量明显低于GES-1细胞株中的miR-204相对表达量(P0.05)。胃癌组组织标本中miR-204相对表达量与患者的年龄、性别无关(P0.05),与TNM分期、淋巴结转移、分化程度有关(P0.05)。第3天的BGC823、SGC7901细胞株中,未转染组的吸光度高于转染miR-204组(P0.05),未转染组的细胞凋亡百分比显著低于转染miR-204组(P0.05)。结论 miR-204在胃癌组织以及胃癌细胞株中呈现低表达,且其表达与TNM分期、淋巴结转移以及分化程度有关,转染miR-204后能抑制胃癌细胞株的细胞增殖,并能促进其细胞凋亡。     

小干扰RNA SOX5对胃癌细胞增殖和凋亡的影响

[目的]探讨Y染色体上的性别决定区相关高迁移率族盒蛋白-5(SOX5)的小干扰RNA(siRNA)对胃癌细胞BGC823增殖及凋亡的影响。[方法]通过qRT-PCR和Western-blot分别检测胃癌细胞系(SGC7901,BGC823,AGS,HGC27)及正常胃上皮细胞GES-1中SOX5 mRNA和蛋白的表达情况;取对数生长周期的胃癌细胞BGC823,通过Lipofiectamine2000将设计合成的SOX5的特异性siRNA以及NC转染BGC823细胞,作为siSOX5组和NC组,不做任何处理的细胞作为空白对照组。qRT-PCR检测各组细胞中SOX5 mRNA的表达情况;Western-blot检测各组SOX5及CyclinD1、P21、Bax、Bcl-2蛋白的表达;MTT检测转染12 h、24 h、48 h、72 h后,各组细胞的增殖情况;流式细胞仪检测转染72 h后各组细胞的凋亡情况。[结果]与正常胃上皮细胞GES-1相比,胃癌细胞SGC7901,BGC823,AGS,HGC27中SOX5 mRNA和蛋白表达升高(P0.05);转染siSOX5后,siSOX5组SOX5 mRNA及蛋白表达降低(P0.05);MTT结果显示:与空白对照组和NC组相比,siSOX5组细胞增殖受到抑制,且CyclinD1蛋白表达水平显著下降,p21蛋白表达显著升高(P0.05);流式细胞检测结果显示:与空白对照组和NC组相比,siSOX5组细胞凋亡率升高,且Bax蛋白表达升高,Bcl-2蛋白表达下降(P0.05)。[结论]干扰SOX5能够降低胃癌BGC823细胞中SOX5的表达,抑制BGC823细胞的增殖并促进凋亡。     

长链非编码RNA核仁小分子RNA宿主基因1对胃癌细胞增殖和侵袭的影响

目的探讨长链非编码(lnc)RNA核仁小分子RNA宿主基因(SNHG)1在胃癌中的表达水平及其对胃癌细胞增殖和侵袭过程的影响。方法实时荧光定量-聚合酶链反应(qRT-PCR)检测SNHG1在胃癌细胞SGC7901、BGC823和正常胃上皮细胞NGEC中的表达水平及采用SUHG1的小干扰RNA(si-SNHG1)干扰后SNHG1的表达水平;噻唑蓝(MTT)法检测沉默SNHG1对SGC7901、BGC823细胞增殖的影响,Transwell小室检测沉默SNHG1对SGC7901、BGC823细胞侵袭能力的影响。Western印迹法检测沉默SNHG1前后增殖标志物Ki67和侵袭相关蛋白基质金属蛋白酶(MMP)-2、MMP-9在SGC7901、BGC823中的表达变化。结果 SNHG1在胃癌细胞株中的表达显著高于正常胃上皮细胞株(P0.05);沉默SNHG1能显著抑制Ki67、MMP-2、MMP-9的表达。结论 lncRNA SNHG1在胃癌细胞中高表达,沉默SNHG1对胃癌细胞的增殖、侵袭起抑制作用,SNHG1可能成为治疗胃癌的一个有效靶点。     

miR-181a、miR-181b在人胃癌细胞和组织中的表达

目的:研究miR-181a、miR-181b在不同分化程度人胃癌细胞株和胃癌组织中的表达情况,探索其在胃癌发生发展过程中的作用.方法:体外培养3种不同分化程度的胃癌细胞株(AGS,SGC-7901、MGC-803)及正常胃黏膜细胞GES-1,收集28例胃癌患者手术切除的癌组织及正常组织样本,通过实时定量聚合酶链反应(quantitative real-time polymerasechain reaction,qRT-PCR)方法检测上述细胞和组织中miR-181a、miR-181b的表达量,比较胃癌细胞与正常胃黏膜细胞、胃癌组织与正常胃组织中miR-181a,miR-181b表达的差异性.结果:经qRT-PCR方法检测发现,AGS、S GC-7901、MGC-803 3种胃癌细胞中miR-181a及miR-181b的表达量均高于GES-1细胞中的表达量(P0.05),而AGS,SGC-7901、MGC-803 3种胃癌细胞之间miR-181a及miR-181b的表达量差异均无统计学意义(P0.05).与正常胃组织相比,miR-181a,miR-181b在胃癌组织中的表达量显著升高(P0.05).Ⅲ/Ⅳ期组胃癌组织中miR-181a,miR-181b的相对表达量高于Ⅰ/Ⅱ期组(P0.05).有淋巴结转移组胃癌组织中miR-181a,miR-181b的相对表达量高于无淋巴结转移组(P0.05).miR-181a,miR-181b的相对表达量与年龄、性别、胃癌的分化程度无明显关系(P0.05).结论:miR-181a、miR-181b在胃癌细胞和组织中高表达,两者的表达水平与胃癌的分期、淋巴结转移相关,可能在胃癌的发生发展中发挥癌基因的作用.     

hCTB006联合伊立替康对胃癌细胞BGC823、SGC7901协同杀伤的作用机制

目的:研究人死亡受体(death receptor5,DR5)激动型抗体hCTB006联合伊立替康对不同分化程度胃癌细胞BGC823、SGC7901的体外抑瘤作用,并对其诱导胃癌细胞凋亡的机制进行初步探讨.方法:实验将BGC823、SGC7901细胞分为伊立替康组、hCTB006组和两者联合应用组,应用ATPlite法研究各组药物的体外抑瘤作用;采用ELISA法研究伊立替康处理胃癌细胞前后DR5表达的变化.采用Western blot技术检测药物处理前后BGC823、SGC7901细胞X-联锁凋亡抑制蛋白(X-chromosome-linked inhibitory of apoptosis protein,XIAP)的表达变化情况.结果:BGC823对hCTB006中度敏感,对SGC7901不敏感,伊立替康对胃癌细胞的增殖抑制作用呈浓度依赖性,与hCTB006联合用药后对BGC823具有良好的协同抑制作用,但对SGC7901协同作用不明显.ELISA测得伊立替康处理后胃癌细胞DR5的表达量无明显变化.但伊立替康和hCTB006联合用药可使胃癌细胞BGC823内XIAP水平明显降低,而对SGC7901细胞内XIAP没有明显作用.结论:伊立替康联合hCTB006后对低分化胃癌细胞BGC823的增殖有明显协同抑制作用,而对中度分化的SGC7901细胞呈拮抗作用,这种诱导胃癌细胞凋亡的机制可能与其DR5的表达无关,而与联合作用后细胞抑凋亡蛋白XIAP的表达水平有关.     

敲低长链非编码RNA LOXL1- AS1表达对胃癌细胞增殖、凋亡的影响及其机制

目的探讨敲低长链非编码RNA LOXL1-AS1表达对胃癌细胞增殖、凋亡的影响,并探讨其可能的作用机制。方法实时荧光定量PCR(qRT-PCR)法检测不同胃癌细胞株(AGS、BGC823、NCI-N87、MGC803和SGC7901)和正常胃黏膜细胞株GES-1中LOXL1-AS1表达情况;选取LOXL1-AS1表达水平最高的胃癌BGC823细胞系,建立LOXL1-AS1敲低模型,实验分为sh-LOXL1-AS1组和sh-NC组,分别转染LOXL1-AS1靶向shRNA和scramble shRNA,qRT-PCR法验证干扰效率,CCK-8检测细胞增殖,流式细胞仪检测细胞凋亡情况,免疫印迹法检测Bcl-2、Bax、PI3K、p-PI3K、Akt和p-Akt表达。结果 qRT-PCR结果显示,与正常胃黏膜细胞GES-1相比,胃癌细胞株中LOXL1-AS1表达水平均显著升高(P0.05)。与sh-NC组比较,sh-LOXL1-AS1组LOXL1-AS1表达水平显著降低(P0.05),细胞增殖率显著降低(P0.05),细胞凋亡率显著升高(P0.05),细胞Bcl-2、p-PI3K和p-Akt表达显著降低,Bax表达显著升高(P0.05)。结论敲低LOXL1-AS1表达可抑制胃癌细胞增殖并促进细胞凋亡,其机制可能与抑制PI3K/Akt信号通路,继而调控凋亡相关蛋白表达,启动细胞凋亡程序有关。     

胃癌细胞对细小病毒H-1敏感性差异的实验研究

目的 探讨不同胃癌细胞株对细小病毒细胞毒作用的敏感性差异及可能的机制。方法共选用HGC27(未分化)、BGC823(未分化)、MKN45(低分化)、AGS(低分化)、SGC7901(中分化)和MKN28(高分化)等6株不同分化状态的胃癌细胞株，用流式细胞仪分析其各自的细胞周期，H-1病毒感染后采用MTT方法检测不同胃癌细胞株对其细胞毒作用的敏感性差异，用RT-PCR来检测H-1病毒中的非结构蛋白基因(NS-1)在6株不同胃癌细胞中的表达。结果 HGC27、BGC823、MKN45、AGS、SGC7901和MKN28等不同分化状态细胞株中，S期细胞的比率分别为24．72％，30．15％，27．10％，29．03％，31．82％和33．73％。其中HGC27细胞对H-1病毒的细胞毒作用敏感；SGC7901细胞其次；MKN45、AGS细胞对H-1病毒的细胞毒作用中等敏感；MKN28细胞对H-1病毒的细胞毒作用不敏感；而BGC823则对H-1病毒的细胞毒作用抵抗。病毒NS-1的mRNA在HGC27、BGC823、MKN45和SGC7901等细胞中的表达水平较高，而在AGS和MKN28中的表达水平却较低。结论 H-1病毒的细胞毒作用在不同的胃癌细胞株中的差异显著。总体上，与高分化细胞株MKN28细胞相比，分化差的细胞对细小病毒H-1的细胞毒作用敏感性增加。其机制至少部分与分化差细胞中病毒NS-1蛋白的产生和积聚能力增高相关。未分化的BGC823细胞对H-1病毒的细胞毒作用抵抗，进一步证实并非所有的肿瘤细胞都对细小病毒的溶胞性作用敏感。     

MicroRNA-133a在5-氟尿嘧啶促进胃癌细胞BGC823及SGC7901细胞凋亡中的功能研究

[目的]研究microRNA-133a(miR-133a)在5-氟尿嘧啶(5-Fu)诱导胃癌细胞BGC823及SGC7901凋亡中的作用。[方法]用荧光定量PCR检测经5-Fu(IC50值)处理过胃癌细胞miR-133a的表达;构建过表达miR-133a的胃癌细胞株并行细胞增殖、细胞流式验证miR-133a的生物学功能;5-Fu分别处理过表达及敲低miR-133a的胃癌细胞株后,行细胞增殖、细胞流式、Western Blot观察细胞生长及凋亡情况。[结果]5-Fu诱导BGC823及SGC7901内源性miR-133a的表达(50%,P0.0001,24h),miR-133a促进胃癌细胞凋亡,敲低miR-133a可以抑制5-Fu对胃癌细胞的促凋亡作用。[结论]5-Fu通过诱导胃癌细胞BGC823及SGC7901内源性miR-133a的表达,促进胃癌细胞凋亡。     

下调Six1基因表达对胃癌细胞生物学特性及B7-H1表达的影响

目的探讨抑制胃癌细胞Six1表达对癌细胞增殖侵袭及B7-H1表达的影响及机制。方法以人正常胃黏膜上皮细胞GES-1为对照细胞,Western印迹检测胃癌MKN45、BGC823和AGS细胞Six1的蛋白表达;参照LipofectamineTM2000转染说明将非特异性siRNA(NC组)和Six1特异性的siRNA(si-Six1组)转染BGC823细胞,并设置空白对照组,转染48 h,通过MTT及Transwell小室分别检测各组细胞活力及侵袭能力;Western印迹检测Six1、B7-H1及JAK2/STAT3信号通路磷酸化的JAK2、STAT3及下游分子细胞周期蛋白(cyclin)D1和基质金属蛋白酶(MMP)-2的蛋白表达。结果胃癌MKN45、BGC823和AGS细胞Six1的表达均显著高于在GES-1细胞表达(P0.05);转染si-Six1的BGC823细胞Six1的蛋白表达显著低于空白对照组(P0.05);与NC组比较,si-Six1组细胞活力及侵袭能力均显著降低,B7-H1、p-JAK2、p-STAT3、cyclinD1和MMP-2的蛋白表达均显著降低(P0.05)。结论下调胃癌细胞Six1表达可降低癌细胞活力及侵袭能力,降低B7-H1表达,机制可能是抑制JAK2/STAT3信号通路。     

GFPT2在胃癌中的表达及作用的研究

目的通过检测胃癌和癌旁正常组织以及5种细胞株中谷氨酰胺果糖-6-磷酸转氨酶2(GFPT2)mRNA和蛋白的表达水平,探讨GFPT2表达与胃癌发生、转移的关系及意义。方法利用实时荧光定量PCR及Western blotting法检测GFPT2在33例患者配对的新鲜胃癌组织和癌旁正常组织(距离肿瘤边缘5 cm)标本、5种细胞株GES、MGC803、MKN45、BGC823及AGS中的表达情况,并利用免疫组织化学技术检测GFPT2在82例患者配对的胃癌及癌旁正常组织石蜡标本中的表达情况。结果 GFPT2 mRNA和蛋白在81.82%(27例)胃癌中呈高表达,且其在伴有肝转移的胃癌组织中的表达水平明显高于不伴有肝转移者。正常胃黏膜上皮细胞株GES中GFPT2 mRNA的表达水平明显低于胃癌细胞株MGC803、MKN45、BGC823和AGS(P0.05);胃黏膜上皮细胞株GES中GFPT2蛋白表达水平低于胃癌细胞株MGC803、MKN45、BGC823(P0.05),但与胃癌细胞株AGS中GFPT2蛋白表达水平差异无统计学意义。高转移潜能细胞株MKN45和BGC823中GFPT2的表达水平明显高于低转移潜能细胞株AGS及MGC803(P0.05)。GFPT2表达水平与胃癌分化程度呈负相关,与远处转移呈正相关(P0.05)。结论 GFPT2在胃癌组织中的表达上调,且与其转移密切相关,推测GFPT2可能具有促进胃癌转移的作用。     

Genome-wide analysis of histone H3 lysine 27 trimethylation by ChIP-chip in gastric cancer patients

Background  Trimethylation of histone H3 lysine 27 (H3K27me3) is a posttranslational modification that is highly correlated with genomic silencing. In gastric cancer (GC), global and gene-specific DNA methylation changes have been demonstrated to occur. However, to date, our understanding of the alterations in H3K27me3 in GC is incomplete. This study aimed to investigate the variations in H3K27me3 in CpG island regions between gastric cancerous and matched non-cancerous tissues. Methods  H3K27me3 variations were analyzed in eight pairs of GC and adjacent normal tissues, from eight GC patients, using a chromatin immunoprecipitation linked to the microarray (ChIP-chip) approach. ChIP–real time PCR was used to validate the microrray results. In addition, DNA methylation status also was further analyzed by methyl-DNA immunoprecipitation quantitative PCR. Results  One hundred twenty-eight (119 increased and 9 decreased H3K27me3) genes displaying significant H3K27me3 differences were found between GC and adjacent normal tissues. The results of ChIP–real time PCR coincided well with those of microarray. Aberrant DNA methylation can also be found on selected randomly positive genes (MMP15, UNC5B, SHH, AFF3, and RB1). Conclusion  Our study indicates that there are significant alterations of H3K27me3 in gastric cancerous tissues, which may help clarify the molecular mechanisms involved in the pathogenesis of GC. Such novel findings show the significance of H3K27me3 as a potential biomarker or promising target for epigenetic-based GC therapies. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. L. Zhang and K. Zhong contributed equally to this report.     

Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27)

Trimethylation of histone H3 on lysine 27 (H3K27me3) is a repressive posttranslational modification mediated by the histone methyltransferase EZH2. EZH2 is a component of the polycomb repressive complex 2 and is overexpressed in many cancers. In B-cell lymphomas, its substrate preference is frequently altered through somatic mutation of the EZH2 Y641 residue. Herein, we identify mutation of EZH2 A677 to a glycine (A677G) among lymphoma cell lines and primary tumor specimens. Similar to Y641 mutant cell lines, an A677G mutant cell line revealed aberrantly elevated H3K27me3 and decreased monomethylated H3K27 (H3K27me1) and dimethylated H3K27 (H3K27me2). A677G EZH2 possessed catalytic activity with a substrate specificity that was distinct from those of both WT EZH2 and Y641 mutants. Whereas WT EZH2 displayed a preference for substrates with less methylation [unmethylated H3K27 (H3K27me0):me1:me2 k(cat)/K(m) ratio = 9:6:1] and Y641 mutants preferred substrates with greater methylation (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1:2:13), the A677G EZH2 demonstrated nearly equal efficiency for all three substrates (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1.1:0.6:1). When transiently expressed in cells, A677G EZH2, but not WT EZH2, increased global H3K27me3 and decreased H3K27me2. Structural modeling of WT and mutant EZH2 suggested that the A677G mutation acquires the ability to methylate H3K27me2 through enlargement of the lysine tunnel while preserving activity with H3K27me0/me1 substrates through retention of the Y641 residue that is crucial for orientation of these smaller substrates. This mutation highlights the interplay between Y641 and A677 residues in the substrate specificity of EZH2 and identifies another lymphoma patient population that harbors an activating mutation of EZH2.     

P27kip1 regulates the apoptotic response of gastric epithelial cells to Helicobacter pylori

BACKGROUND: Helicobacter pylori infection increases the risk of gastric cancer but the molecular mechanisms responsible are not well understood. Gastric cells chronically exposed to H pylori in vitro develop resistance to apoptosis associated with low levels of p27, a cyclin dependent kinase inhibitor and haplo insufficient tumour suppressor gene that is downregulated in gastric cancer. AIM: To determine whether the low level of p27 protein is responsible for the resistance to apoptosis of gastric cancer cells. METHODS: The effects of increasing the expression of p27 protein were examined by transiently and stably transfecting a plasmid encoding full length p27 mRNA into apoptosis resistant gastric cancer cell lines with low p27 expression that were derived from AGS gastric cancer cells by chronic H pylori coculture followed by dilutional cloning. RESULTS: Low p27 expression in the apoptosis resistant derivative cell lines was associated with an approximate 30% decrease in p27 mRNA and an 80% decrease in p27 protein that was not due to increased proteasome dependent degradation of p27 protein. Transient or stable transfection with p27 constructs partially restored the sensitivity of the apoptosis resistant cells to 5-fluorouracil and H pylori induced apoptosis without altering spontaneous apoptotic cell death. CONCLUSIONS: These results demonstrate that p27 positively regulates, at least in part, the apoptotic response of gastric epithelial cells to H pylori. Low gastric p27 may promote gastric carcinogenesis associated with H pylori infection by inhibiting apoptotic pathways.     

The PARP inhibitor PJ34 modifies proliferation,NIS expression and epigenetic marks in thyroid cancer cell lines

Since PARP-1 is supposed to be part of a multimeric repressor of sodium iodide symporter (NIS) expression, in this study the effect of the PARP inhibitor PJ34 on several properties of thyroid cancer cell lines was investigated. In TPC1, BCPAP, FRO, WRO cell lines PJ34 induced a strong increase in NIS mRNA levels. In BCPAP and TPC1 cells also significant increase of radio-iodine uptake was induced. Accordingly, in transfection experiments performed in TPC1 cells, treatment with PJ34 increased NIS promoter activity without affecting PARP-1 binding to the promoter sequence. We also investigated the epigenetic status of NIS promoter after PJ34 treatment in TPC1 cell line: in addition to an increase of histone modification activation marks (H3K9K14ac, H3K4me3), surprisingly we observed also an increase of H3K27me3, a classical repressive mark.     

Up-regulation of PIK3CA promotes metastasis in gastric carcinoma

AIM:To explore expressions of PIK3CA in the progression of gastric cancer from primary to metastasis and its effects on activation of phosphatidylinositol 3-kinase(PI3K)/Akt pathway.METHODS:mRNA and protein levels of PIK3CA were assessed,respectively,by real-time quantitative polymerase chain reaction and immunohistochemistry in specimens of normal gastric mucosa,primary foci and lymph node and distant metastasis of gastric cancer.Akt and phosphorylated Akt protein were also examined by Western blotting in these tissues,in order to analyze the effect of PIK3CA expression level changes on the activation of PI3K/Akt signaling pathway.RESULTS:PIK3CA mRNA in lymph node metastasis were approximately 5 and 2 folds higher,respectively,than that in the corresponding normal gastric mucosa and primary gastric cancer tissues(P<0.05),while no statistical significance was found compared with distant metastasis.Immunohistochemically,PIK3CA protein expression was discovered in 7(35%)specimens of 20 primary foci vs 10(67%)of 15 of lymph node metastasis or 11(61%)of 18 of distant metastasis(35%vs 67%,P=0.015;35%vs 61%,P=0.044).With the increased level of PIK3CA expression,the total Akt protein expression remained almost unchanged,but p-Akt protein was upregulated markedly.CONCLUSION:Increased expression of PIK3CA is expected to be a promising indicator of metastasis in gastric cancer.Up-regulation of PIK3CA may promote the metastasis of gastric cancer through aberrant activation of PI3K/Akt signaling.     

RNAi knockdown of PIK3CA preferentially inhibits invasion of mutant PIK3CA cells

AIM: To explore the effects of siRNA silencing of PIK3CA on proliferation, migration and invasion of gastric cancer cells and to investigate the underlying mechanisms. METHODS: The mutation of PIK3CA in exons 9 and 20 of gastric cancer cell lines HGC-27, SGC-7901, BGC-823, MGC-803 and MKN-45 was screened by polymerase chain reaction (PCR) followed by sequencing. BGC-823 cells harboring no mutations in either of the exons, and HGC-27 cells containing PIK3CA mutations were employed in the current study. siRNA...     

白细胞介素-1β介导幽门螺杆菌相关胃癌发生的实验研究

目的 探讨白细胞介素(IL)-1β在幽门螺杆菌(Hp)相关胃癌发生中可能的作用机制.方法 以人胃永生化上皮细胞株(GES-1)和胃癌细胞株(AGS)为研究对象,采用四甲基偶氮唑盐比色法测定IL-1β对细胞增殖的影响,流式细胞术碘化丙啶单染法测定IL-1β对Hp(NCTC 11637)诱导细胞凋亡的影响.分别应用RT-PCR法和流式细胞术(荧光定量法)检测IL-1β对细胞环氧合酶-2(COX-2)mRNA和蛋白表达的影响.以兔离体壁细胞为研究对象,应用14C-氨基比林(14C-AP)摄取法检测IL-1β对组胺刺激壁细胞酸分泌的影响,应用RT-PCR法分析IL-1β对壁细胞H+-K+-ATP酶α亚基mRNA表达的影响.结果 IL-1β能刺激GES-1和AGS细胞增殖,抑制Hp诱导的GES-1和AGS细胞凋亡.IL-1β能诱导GES-1 COX-2表达,上调AGS细胞COX-2表达;诱导GES-1和AGS细胞COX-2蛋白表达上调(分别由1.016±0.020和1.070±0.034上调至1.485±0.220和1.501±0.182).IL-1β能抑制组胺刺激的离体壁细胞酸分泌,同时伴H+-K+-ATP酶α亚基mRNA表达下调.结论 IL-1β可能通过两条途径在Hp相关胃癌发生中起作用:上调COX-2表达,破坏胃上皮细胞增殖、凋亡平衡和下调H+-K+-ATP酶表达以抑制壁细胞分泌.