葡萄糖影响丁酸钠诱导结肠癌细胞凋亡和增殖抑制作用及其可能机制

目的观察葡萄糖对丁酸钠诱导结肠癌细胞凋亡和增殖抑制作用效果的影响,并探讨这种影响的可能机制。方法细胞生存率的检测采用MTT法,流式细胞仪法检测细胞凋亡。RT-PCR方法检测单羧酸转运蛋白1（MCT1）和葡萄糖转运蛋白1（GLUT1）mRNA的表达情况。结果低葡萄糖浓度培养条件下可以诱导结肠癌细胞HT-29凋亡,并影响其生长,且葡萄糖能够明显抵制丁酸钠诱导凋亡和增殖抑制作用,同时葡萄糖轻度抑制GLUT1 mRNA表达,对MCT1 mRNA也有一定抑制作用。结论葡萄糖浓度变化能够明显影响丁酸钠诱导凋亡和增殖抑制作用,这种影响可能与葡萄糖和丁酸钠在细胞内浓度变化有关。     

葡萄糖转运蛋白在丁酸钠诱导结肠癌细胞凋亡中的作用

目的观察丁酸钠对结肠肿瘤细胞HT-29葡萄糖转运蛋白(GLUT1～GLUT5)表达的影响以及丁酸钠和不同浓度葡萄糖对bax和bcl-x/l表达的影响,探讨丁酸钠诱导肿瘤细胞凋亡的可能机制。方法2005年4月至12月在武汉大学人民医院应用逆转录-聚合酶链反应(RT-PCR)检测GLUT1～GLUT5mRNA的表达情况。免疫细胞化学法检测bax和bcl-x/l的表达。原位切口末端标记法(Tunel)检测细胞凋亡。结果丁酸钠明显抑制GLUT1和bcl-x/l表达并诱导肿瘤细胞凋亡,但对GLUT2、GLUT3、GLUT5和bax表达影响不大,GLUT4则未被检测出。丁酸钠干预条件下,葡萄糖浓度增加可以明显增加bcl-x/l的表达并降低丁酸钠诱导的细胞凋亡。无丁酸钠干预条件下,葡萄糖浓度变化对细胞凋亡影响很小。结论在HT-29细胞中,丁酸钠能明显降低GLUT1的表达。降低GLUT1的表达与丁酸钠诱导细胞凋亡作用密切相关。     

Zebularine联合丁酸钠对结肠癌细胞系LOVO增殖、凋亡以及P16基因表达的影响

目的探讨Zebularine和丁酸钠对结肠癌LOVO细胞增殖、凋亡及P16基因表达的影响。方法培养人结肠癌细胞系LOVO,分为4组:阴性对照组、Zebularine组、丁酸钠组、Zebularine+丁酸钠组。四甲基偶氮唑蓝(MTT)法检测细胞处理24 h、48 h、72 h后的增殖状况,Annexin V-FITC/PI双染法检测细胞凋亡,逆转录聚合酶链反应(RT-PCR)检测P16基因的表达。结果 Zebula-rine组和丁酸钠组LOVO细胞的抑制率和凋亡率与对照组相比显著增高,Zebularine+丁酸钠组细胞抑制率和凋亡率均显著高于单独用药组(P<0.05);Zebularine组和丁酸钠组P16 mRNA相对表达量显著高于对照组(P<0.05),Zebularine+丁酸钠组P16 mRNA相对表达量显著高于各单独用药组和对照组(P<0.05)。结论与单独用药相比,Zebularine联合丁酸钠可以明显促进P16 mRNA的表达,抑制结肠癌细胞生长。     

丁酸钠对结肠癌细胞株HT-29血管内皮生长因子表达水平的影响

目的 观察丁酸钠对结肠癌细胞株HT-29的生长抑制情况以及对血管内皮生长因子(VEGF)表达水平的影响。方法 运用细胞增生抑制实验(MTT法)，免疫细胞化学技术观察丁酸钠对HT-29细胞株的生长和对、VEGF表达水平的影响。结果 丁酸钠能抑制HT-29细胞株增生，并降低VEGF表达水平。结论 丁酸钠能够降低VEGF的表达水平，提示可用作抗血管生成物质降低肿瘤细胞侵袭力。     

NaB对人卵巢上皮癌细胞株3AO 增殖和凋亡的影响

目的 探讨丁酸钠（NaB）对人卵巢上皮癌细胞株3AO增殖和凋亡的影响及其作用机制。方法 用不同浓度NaB对3AO细胞作用不同时间,观察其对3AO细胞增殖活性的影响,分析细胞周期、DNA含量和细胞凋亡率的变化。结果 随培养时间延长,NaB浓度≥4mmol／L时．3AO细胞皱缩,数量渐减,同一NaB浓度下,3AO细胞增殖抑制率随作用时间的延长有增加趋势;NaB浓度为4mmol／L、8mmol／L、12mmol／L时,对3AO细胞增殖有明显抑制作用;NaB作用72h,随浓度升高,增殖细胞核抗原（PCNA）阳性细胞百分率逐渐下降,与对照组相比差异有显著性,P〈0．05。NaB作用24h开始出现细胞周期阻滞,随浓度增高,G1期细胞增多,S期细胞减少,作用48h,出现细胞凋亡峰;增加NaB浓度或相同浓度增加作用时间,凋亡峰增高。结论 NaB呈剂量、时间依赖模式影响卵巢上皮癌细胞株3AO的体外增殖,可能通过G1期阻滞诱导卵巢上皮癌细胞凋亡。     

丁酸钠和5-aza诱导间充质干细胞向心肌细胞分化的研究

目的探讨组蛋白去乙酰化酶抑制剂丁酸钠（sodiumbutyrate）和DNA甲基化抑制剂5-aza对骨髓间充质干细胞（BMSCs）向心肌细胞分化的影响。方法常规培养大鼠BMSCs,细胞分为4组：依次加入丁酸钠0mM,0.5mM,1.0raM,2.0mM。MTT和流式细胞仪检测不同浓度丁酸钠对细胞增殖和凋亡的影响。4周后利用western blot和免疫荧光检测4组细胞的心肌细胞特异性蛋白的表达。从上述4组中选出诱导能力最强的丁酸钠组与5-aza组成4个实验组：阴性对照组,5-aza组,丁酸钠组,5-aza.L丁酸钠组。作用4周后检测心肌细胞特异性蛋白的表达。结果丁酸钠抑制细胞增殖,具有浓度依赖性,而对细胞凋亡没有明显影响。检测发现丁酸钠和5-a．za均能有效诱导BMSCs分化为心肌细胞,丁酸钠诱导分化最适浓度为1.0mM。同时1．0mM丁酸钠诱导分化效率高于5-aza。除此,5-aza和丁酸钠共同作用于BMSCs,其诱导分化能力明显高于其它组。结论丁酸钠能够有效诱导BMSCs向心肌细胞分化,丁酸钠浓度为1．0mM时诱导能力最强,同时诱导分化率高于5-aza。5-aza和丁酸钠一起作用诱导BMSCs向心肌细胞分化的能力明显高于其它组,间接证明DNA去甲基化和组蛋白乙酰化具有协同作用。丁酸钠在有效作用浓度范围内,虽然抑制BMSCs增殖,但是不影响细胞凋亡,表明丁酸钠具有低毒的特性,为以后丁酸钠应用于临床打下实验基础。     

阿魏酸钠抑制高糖诱导的系膜细胞增殖

目的 探讨阿魏酸钠(SF)对高糖诱导的原代培养系膜细胞(GMC)增殖的作用及其机制.方法 原代培养肾小球系膜细胞,分为正常组、甘露醇组、高糖组、高糖加不同浓度SF组,分别于处理后24、48 h收集细胞.用MTT法检测细胞增殖;流式细胞术测定cyclinD1和细胞周期;免疫细胞化学检测p53蛋白的表达.结果 48 h内,高糖促进GMC增殖,使GMC由G1期进入S期细胞比例增高;同时cyclinD1蛋白表达上调而p53蛋白的表达减少;SF能明显对抗高糖的这种作用,其作用随SF浓度的增加、作用时间的延长而加强.结论 SF可能通过抑制cyclinD1蛋白表达和促进p53蛋白生成,从而抑制高糖诱导的GMC增殖.     

A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon

AIMTo develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon.METHODSOne-gram sodium butyrate coated tablets containing 13C-butyrate were orally administered to 12 healthy subjects and 12 Crohn's disease patients and the rate of 13C-butyrate absorption was evaluated by 13CO2 breath test analysis for eight hours.Tauroursodeoxycholic acid(500 mg)was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration.RESULTSThe coated formulation delayed the 13C-butyrate release by 2-3 h with respect to the uncoated tablets.Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn's disease patients than in healthy subjects.The variability of the peak 13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time.However,the coating chosen ensured an efficient release of the active compound even in patients with a short transit time.CONCLUSIONSimultaneous evaluation of breath 13CO2 and tauroursodeoxycholic acid concentrationtime curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn's disease patients with variable intestinal transit time.This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.     

艾塞那肽抑制高糖诱导内皮细胞凋亡的作用机制

在正常糖浓度(5.5 mmol/L)和高糖(33 mmol/L)培养的人脐静脉内皮细胞(HUVECs)分别加入不同浓度的艾塞那肽并干预不同时间后,噻唑蓝(MTF)法检测细胞活力,应用流式细胞仪检测细胞早期凋亡率,Western印迹法检测蛋白激酶B(Akt)磷酸化、Bcl-2和Bax蛋白表达水平.结果显示,HUVECs经高糖培养48和72 h后,细胞活力明显下降(P＜0.01).经1、10和100 nmol/L艾塞那肽干预48 h后,细胞活力明显增加,并呈浓度依赖性(P＜0.01).与正常糖浓度组比较,高糖组细胞凋亡率升高,Akt磷酸化和Bcl-2蛋白表达水平下降,Bax蛋白表达增加,Bcl-2/Bax比值降低(P＜0.01).艾塞那肽干预后,细胞凋亡率下降,Akt磷酸化和Bcl-2蛋白表达增加,Bax蛋白表达下降,Bcl-2/Bax比值升高(P＜0.01),而艾塞那肽的作用可被磷酸肌醇3激酶(PI3K)抑制剂LY294002所对抗(P＜0.01).提示艾塞那肽可通过PI3 k/Akt信号通路调节Bcl-2/Bax蛋白表达来抑制高糖诱导的内皮细胞凋亡,起到保护内皮细胞的作用.     

丁酸钠对DMH诱导大鼠肠道肿瘤的作用

目的:观察1,2-二甲基肼(1,2-dimethy lhydrazine,DMH)是否可以诱导出小肠肿瘤,并与大肠进行比较.并探讨丁酸钠(sodium butyrate,NaBt)对DMH诱导肠道肿瘤的作用.方法:实验动物用SPF级♂Wistar大鼠,大小为8-9周龄,共分4组:DMH组、DMH+NaBt组、NaBt组、对照组.实验30-32wk之后过量麻醉使大鼠安乐死,取出小肠和大肠,观察肿瘤部位、数量、大小等;然后用10%甲醛固定,制作病理切片,观察各部位组织学改变.结果:实验结束时DMH组大鼠死亡率60.00%(18/30),DMH+NaBt组死亡率48.00%(12/25).DMH组肠道肿瘤发生率66.67%(8/12),4只肿瘤单发,4只多发,荷瘤率1.33(16/12),小肠肿瘤4个,大肠肿瘤12个;DMH+NaBt组肠道肿瘤发生率84.62%(11/13),6只为单发肿瘤,5只多发,荷瘤率1.46(19/13),小肠肿瘤3个,大肠肿瘤16个.两组之间肿瘤发生率及荷瘤率均无统计学差异.无论是DMH组还是DMH+NaBt组,结肠肿瘤发生率都高于小肠肿瘤,统计学有显著性差异(75.00%vs25.00%,P<0.05;84.21%vs15.79%,P<0.01).DMH组中肿瘤平均体积>0.05cm3个数占37.5%;DMH+NaBt组中肿瘤平均体积>0.05cm3个数占73.68%,两组肿瘤大小有统计学差异(37.50%vs73.68%,P<0.05).与DMH+NaBt组相比,DMH组浸润深度多局限于黏膜层内,有统计学差异(43.75%vs10.53%,P<0.05).结论:DMH也可诱导大鼠小肠肿瘤的发生,但发生率明显低于大肠肿瘤;NaBt可能促进肿瘤生长,关于NaBt对DMH诱导的肠道肿瘤作用仍需做进一步的深入研究.     

单羧酸转运蛋白基因对肿瘤细胞内pH值及生长特性的调节作用

目的 以反义技术抑制肿瘤细胞的单羧酸转运蛋白基因第一亚型(MCT1)表达,观察其对肿瘤细胞内pH值(pHi)调节、乳酸转运及生长性质的影响.方法 (1)应用逆转录-聚合酶链式反应(RT-PCR)从人肺癌细胞系A549中扩增MCT1目的 基因片段,将克隆的基因片段反向插入逆转录病毒载体pLXSN,构建反义表达重组载体pLXSN-MCT1,并对其进行DNA测序验证.(2)通过电穿孔法将pLXSN、重组载体pLXSN-MCT1转染于肺腺癌细胞系A549中,经G418筛选转染细胞阳性克隆.用PCR方法 鉴定pLXSN-MCT1重组载体在基因组的转染整合及表达;以分光光度法测定细胞内pH及乳酸含量变化,并以细胞生长曲线研究细胞的生长情况.结果 (1)对所构建的重组载体进行双酶切电泳分析及DNA序列分析证明反义载体构建成功.(2)与未转染的A549细胞比较,转染MCT1反义表达重组体的细胞pHi降低、乳酸显著升高(P＜0.001);且细胞的生长受到明显抑制.结论 单羧酸转运蛋白MCT1基因在肿瘤细胞pHi调节、乳酸转运及细胞的生长中起着重要的调节作用.     

胰升血糖素样肽-1改善波动性高糖诱导大鼠胰岛细胞增殖功能机制的研究

目的 研究胰升血糖素样肽-1 （GLP-1）对波动性高糖诱导大鼠胰岛细胞增殖功能的影响及机制. 方法 将获取的原代胰岛细胞分为5组,即正常葡萄糖（5.5 mmol/L）组、恒定高糖（30.0 mmol/L）组、波动高糖（每24 h轮换培养于5.5、30.0 mmol/L）组、恒定高糖＋GLP-1 （100 nmol/L）组和波动高糖＋GLP-1组.干预7d后检测细胞增殖活性、活性氧簇（ROS）、细胞周期及周期蛋白cyclinD1、p21、p27、Skp2的表达. 结果 GLP-1干预可降低波动性高糖诱导的细胞内ROS水平[（194.40±19.20）vs（406.78±18.40）,P＜0.05],上调促细胞周期cyclinD1、Skp2表达,下调周期抑制蛋白p21、p27表达,使停滞在G0/G1期的细胞比例减少,改善细胞增殖活性[（1.38±0.09）vs（0.44±0.10）,P＜0.05]. 结论 GLP-1可通过降低氧化应激水平及对不同细胞周期蛋白表达的调节改善波动性高糖抑制的胰岛细胞增殖活性.     

Expression of the brain-type glucose transporter is restricted to brain and neuronal cells in mice

Summary Northern blot analysis of human tissues has demonstrated the expression of the brain-type glucose transporter isoform (GLUT 3) in liver, muscle and fat, raising the possibility that this transporter isoform may play a role in the regulation of glucose disposal in these tissues in response to insulin. We have raised an anti-peptide antibody against the C-terminal 13 amino acids of the murine homologue of this transporter isoform, and determined its tissue distribution in mouse tissues and murine-derived cell lines. The antibodies recognise a glycoprotein of about 50 kilodaltons, expressed at high levels in murine brain. In contrast to human tissues, the expression of GLUT 3 in mice is restricted to the brain, and no immunoreactivity was observed in either liver, fat or muscle membranes, or in murine 3T3-L1 fibroblasts or adipocytes. In contrast, high levels of expression of this isoform were observed in the NG 108 neuroblastoma x glioma cell line, a hybrid cell derived from rat glioma and mouse neuroblastoma cells. Taken together, these data suggest that the expression of GLUT 3 in rodents is restricted to non-insulin responsive neuronal cells and hence it is likely that the factors regulating the expression of this transporter in rodents differ to those in humans.     

康莱特抑制结肠癌细胞转移的作用及其分子机制研究

目的以康莱特(KLT)、环磷酰胺(CTX)抑制癌细胞LoVo细胞增殖、迁移,观察对骨桥蛋白(OPN)、基质金属蛋白酶-9(MMP-9)和尿激酶型纤溶酶原激活物(uPA)表达的影响。方法培养人结肠癌LoVo细胞,取处于对数生长期细胞悬液200μL(细胞浓度为5×104/mL)接种,加入不同体积浓度的KLT或CTX培养,以MTT法检测细胞毒副作用;以Transwell小室检测细胞迁移能力;以Western blotting法分析OPN、MMP-9和uPA变化。结果 KLT、CTX抑制LoVo细胞增殖呈时间、剂量依赖性,其IC50 KLT为20μL/mL,CTX为2μM。在CTX、KLT组细胞存活率分别为57%、63%,比对照组均显著降低(x2值分别为54.78、45.90,P均<0.05)。CTX+KLT组细胞存活率为38%,比CTX、KLT组显著降低(x2值分别为7.29、12.50,P均<0.05)。细胞迁移力:空白组细胞数为117±3.5,CTX组为45±1.3,KLT组为67±2.1,比对照组明显减少(t值分别为43.12、27.89,P均<0.05)。CTX+KLT组为21±0.9,比CTX、KLT组显著减少(t值分别为33.94、45.02,P均<0.05)。KLT下调LoVo细胞OPN、MMP-9和uPA表达,并呈现剂量依赖性。与空白对照组、KLT组及CTX组比,KLT联合CTX组抑制LoVo细胞OPN、MMP-9和uPA的表达更明显。结论 KLT可能通过下调OPN、MMP-9及uPA表达,抑制LoVo细胞增殖和转移,且与CTX联合具有协同作用。     

辣椒素促进大肠癌细胞凋亡作用机制的研究

目的观察辣椒素对大肠癌细胞增殖和凋亡的作用,进一步了解其作用机制是否参与经典Wnt信号通路和(或)非经典Wnt信号通路。方法用免疫组化染色法显示大肠癌细胞Ls174是否表达COX-2、β-catenin、STAT3、AP-1。不同浓度梯度的辣椒素在不同时间点24 h、48 h、72 h作用于大肠癌细胞后,用MTT法观察其对大肠癌细胞增殖率的影响,同时用流式细胞仪检测其对大肠癌细胞凋亡率的影响。用荧光定量PCR仪分别检测基因COX-2、β-catenin、STAT3、AP-1 mRNA的表达量在辣椒素对其作用前后的变化。结果免疫组化染色法显示大肠癌细胞Ls174中,COX-2、β-catenin、STAT3、AP-1均呈阳性表达。辣椒素可下调COX-2和β-catenin mRNA的表达。200~400μmol/L辣椒素作用大肠癌细胞24~48 h后COX-2 mRNA下调为对照组的18.0%~89.0%,β-catenin mRNA下调为对照组的21.6%~81.9%,且下调幅度随辣椒素浓度的加大及作用时间的延长而增强。STAT3的表达在24~48 h内则增加了20.0%~100%。而AP-1的表达则无明显变化。MTT法检测显示其对细胞增殖的影响呈时间和浓度依赖。100~400μmol/L辣椒素作用细胞24 h,细胞增殖的抑制率由4.5%增至59.0%,延长至48 h后抑制率为65.0%~87.0%,与对照组相比,差异有统计学意义(P0.05)。流式细胞仪检测的细胞凋亡率随浓度及时间延长也呈现出依赖性,且细胞周期G1期由28.0%上调至40.0%,而S期则由58.0%下调至34.5%。结论辣椒素在抑制大肠癌细胞增殖的同时促进细胞的凋亡,其作用呈时间和浓度依赖。     

Changes of antigen expression on human hepatoma cell lines caused by sodium butyrate,a differentiation inducer

We have previously reported the effect of a differentiation inducer, sodium butyrate (SB), on human hepatocellular carcinoma (HCC) cell lines, demonstrating that it was a potent inducer of differentiation. In the present study, we investigated the alteration in expression of an antigen defined by a murine monoclonal antibody, H2, as well as alterations in the expression of other antigens, on the HCC cell lines HCC-T, HCC-M, and PLC/PRF/5, since it is known that specific antigenic changes occur during the differentiation of leukemic cells. The expression of the antigen defined by H2 increased immunocytochemically on HCC-T, HCC-M, and PLC/PRF/5 during treatment with SB. A flowcytometric study showed that almost all the HCC-T and HCC-M cells treated with SB highly expressed this antigen after 5 days' treatment. The antigen expression detected by H2 decreased after the removal of SB from the medium. On the other hand, antigen expression detected by another monoclonal antibody, 5C11, was not changed by this treatment. The expression of intracellular adhesion molecule (ICAM)-1 in HCC-T increased slightly, but that of β2-microglobulin and HLA-DR did not change. These results demonstrated that some antigen expression was changed by SB treatment and that the antigen defined by H2 seemed to be highly expressed on human HCC cells in the differentiated state.     

青蒿琥酯对人结肠癌HCT-8细胞诱导血管新生的影响及机制探讨

目的观察青蒿琥酯对人结肠癌HCT-8细胞诱导血管新生的影响,并探讨其作用机制。方法采用大鼠主动脉环体外培养实验和鸡胚绒毛尿囊膜体内血管生长实验观察青蒿琥酯对人结肠癌HCT-8细胞诱导血管新生的影响。采用Western blot法检测青蒿琥酯作用前后人结肠癌HCT-8细胞的血管内皮生长因子(VEGF)、血管生成素-2(Ang-2)蛋白。结果青蒿琥酯可明显减少HCT-8细胞诱导的血管生成。HCT-8细胞高表达VEGF、Ang-2蛋白,青蒿琥酯呈剂量依赖方式下调HCT-8细胞VEGF、Ang-2蛋白的表达(P均<0.05)。结论青蒿琥酯具有抗人结肠癌HCT-8细胞诱导血管新生的效应,与青蒿琥酯抑制HCT-8细胞的VEGF、Ang-2蛋白表达有关。     

Effects of a sodium glucose co‐transporter 2 selective inhibitor,ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Aims/Introduction

To assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.

Materials and Methods

We administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.

Results

Continuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 ± 54 mg/dL to 141 ± 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of β-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 ± 0.5 vs 0.5 ± 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively.

Conclusions

The ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss.     

二甲双胍对高葡萄糖环境下结肠癌细胞增殖和侵袭的影响

目的观察二甲双胍在高葡萄糖环境下对人结肠癌细胞系SW480增殖和侵袭的影响,并探讨其可能的机制。 方法通过Western blot方法检测SW480细胞在高葡萄糖及不同浓度二甲双胍干预后E-cadherin和Vimentin的表达水平,并应用CCK-8法及Transwell侵袭实验检测细胞增殖及侵袭能力的变化。 结果高葡萄糖作用不同时间后均能促进结肠癌细胞增殖,二甲双胍能抑制结肠癌细胞的增殖,并呈时间——剂量依赖性。20 mmol/L浓度二甲双胍干预48 h后,Transwell侵袭实验结果显示细胞穿膜数为（40.18±2.22）%,明显低于高糖组和对照组（F=49.403,P<0.001）;Western blot结果显示E-cadherin表达明显增强,Vimentin表达明显减弱。 结论高葡萄糖环境能促进结肠癌细胞生长,二甲双胍能明显抑制有或无高葡萄糖环境下结肠癌的增殖和侵袭能力,其机制可能与调节上皮——间质转化（EMT）过程有关。