miR-567在胰腺癌细胞中的表达及其作用机制

目的:探讨miR-567在胰腺癌细胞中的表达及其作用。方法:采用qRT-PCR检测正常胰腺导管上皮细胞系HPDE6-C7及胰腺癌细胞系Panc-1、AsPC-1、HPAC、BxPC-3中miR-567表达。Panc-1细胞转染miR-567过表达慢病毒载体后,分别用CCK-8法、流式细胞术、划痕愈合实验、qRT-PCR、Western blot法检测细胞增殖、凋亡及迁移能力,以及KPNA4 mRNA与蛋白的表达、凋亡相关蛋白表达的变化。结果:miR-567在胰腺癌细胞系Panc-1、AsPC-1、HPAC、BxPC-3中的表达水平均明显低于正常胰腺导管上皮细胞系HPDE6-C7(均P0.05);miR-567慢病毒转染Panc-1细胞后,增殖能力明显减弱,凋亡率明显增加,划痕愈合率明显降低、KPNA4 mRNA与蛋白表达明显下调、而caspase-3及Bax蛋白表达明显上调(均P0.05)。结论:miR-567在胰腺癌细胞中表达降低,升高其表达可抑制胰腺癌细胞的生长与迁移能力,其机制可能与下调KPNA4并上调凋亡相关蛋白表达有关。     

胰腺星状细胞通过白细胞介素-22影响胰腺癌侵袭转移及化疗耐药的研究

目的探讨具有不同白细胞介素-22(IL-22)表达水平的胰腺星状细胞(PSC)对胰腺癌细胞侵袭转移及化疗耐药的影响。方法将人原代胰腺癌间质PSC细胞与胰腺癌PANC-1细胞共培养后检测IL-22的表达及胰腺癌细胞的生长增殖能力、迁移和侵袭能力变化;构建稳定敲低或者过表达IL-22的人原代胰腺癌间质PSC细胞并与胰腺癌PANC-1细胞进行体外共培养, 检测PANC-1细胞的生长增殖、迁移和侵袭能力;利用稳定敲低或者过表达IL-22的人原代胰腺癌间质PSC细胞并与胰腺癌PANC-1细胞进行体外共培养后检测E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)的表达情况;将含有不同表达水平的胰腺癌间质PSC细胞与胰腺癌PANC-1细胞体外共培养并加入不同浓度梯度的吉他西滨培养72 h后检测细胞存活率, 计算细胞耐受吉他西滨的半数抑制浓度(IC50);将稳定敲低或者过表达IL-22的人原代胰腺癌间质PSC细胞并与胰腺癌PANC-1细胞进行混合后种植于裸鼠皮下, 40 d后处理裸鼠取出肿瘤并绘制肿瘤生长曲线, 比较两组细胞的成瘤能力。采用t检验分析各组间差异的显著性。结果单纯PANC...     

TAp63在胰腺癌中的表达及意义

目的:探讨TAp63在胰腺癌中的表达及其意义。方法:分别real-time PCR和Western blot检测TAp63 m RNA与蛋白在21例胰腺癌及其配对癌旁组织、3种胰腺癌细胞(PANC-1、CFPAC-1、Bx PC3)及正常胰腺细胞(HPDE6-C7)中的表达;用TAp63-si RNA转染PANC-1细胞后,观察TAp63 m RNA与蛋白表达的变化,并用MTT和Brd U法检测转染后PANC-1细胞的增值情况。结果:胰腺癌组织中TAp63 m RNA表达量明显低于癌旁正常胰腺组织(t=2.572,P=0.0158);TAp63m RNA与蛋白在3种胰腺癌细胞株中的表达量均明显低于正常胰腺HPDE6-C7细胞(均P0.05)。与未处理的PANC-1细胞比较,转染TAp63-si RNA后的PANC-1细胞TAp63 m RNA与蛋白明显降低,但细胞增殖与DNA合成能力均明显增强(均P0.05)。结论:TAp63在胰腺癌组织与细胞中表达降低,且表达量越低,细胞生长能力越强。     

含三方基序54调控胰腺癌增殖、侵袭和转移的机制

目的探讨含三方基序54(TRIM54)在胰腺癌中的调控机制。方法胰腺癌细胞株(ASPC-1、BXPC-3、MIA-PaCa-2、PANC-1、SW1990)和正常胰腺上皮导管细胞(HPDE)株购自美国模式培养物集存库(ATCC)。采用实时荧光定量聚合酶链反应(RT-PCR)和蛋白质免疫印迹法(Western blot)检测TRIM54在人胰腺导管上皮细胞(HPDE)和胰腺导管腺癌(PDAC)细胞中的表达。通过转染质粒(shRNA)敲低TRIM54的表达。细胞计数试剂盒(CCK-8)检测细胞的增殖能力。Transwell和细胞划痕实验检测细胞侵袭迁移能力的变化。两组之间的比较采用独立样本t检验, 多组样本之间的比较采用方差分析。结果通过RT-PCR检测, HPDE中TRIM54信使RNA(mRNA)表达水平明显低于胰腺癌细胞(ASPC-1、BXPC-3、MIA-PaCa-2、PANC-1、SW1990)(1.00±0.02比2.05±0.04比1.37±0.03比1.62±0.02比3.18±0.10比3.59±0.07, F=1 042.04, P<0.05)。Western b...     

长链非编码RNA LINC00606对胰腺癌细胞增殖、侵袭及迁移的影响

目的 探讨长链非编码RNA（lncRNA）LINC00606对胰腺癌细胞增殖、侵袭及迁移的影响。方法 （1）利用转录组测序技术检测3组胰腺癌组织与癌旁组织中的lncRNA表达水平,经对比分析筛选出目标lncRNA LINC00606。（2）采用PCR检测LINC00606在3种胰腺癌细胞系（BxPC-3、PANC-1、SW1990）和正常胰腺导管上皮细胞系（HPDE6c-7）中的表达。（3）通过oeRNA过表达质粒上调PANC-1细胞中LINC00606的表达水平,然后将其分为未转染组（Ctrl）、转染pcDNA3.1空载体组（Vector组）和转染重组质粒 pcDNA3.1组（oe-LINC 00606）;下调BxPC-3细胞中LINC00606水平,然后将其分为未转染组（Ctrl组）、转染空白（shNC组）及转染组（sh-LINC 00606组）;采用RT-qPCR检测各组细胞中LINC00606的表达水平;运用平板克隆实验检测细胞克隆形成数,细胞划痕实验检测划痕愈合相对百分比,Transwell实验研究检测细胞侵袭迁移能力。结果 （1）胰腺癌组织中 LINC00606的表达显著降低（P<0.05）;（2）胰腺癌细胞中LINC00606表达水平显著降低（P<0.05）;（3）与Vector组相比,oe-LINC 00606组细胞克隆形成数、划痕愈合相对百分比、细胞迁移和侵袭数量降低（均P<0.05）;与shNC组相比,sh-LINC00606组细胞克隆形成数、划痕愈合相对百分比、细胞迁移和侵袭数升高（P<0.05）。结论 LINC00606低表达可促进胰腺癌细胞的增殖、侵袭及迁移能力,在胰腺癌发生发展过程中可能起着重要的调节作用。     

长链非编码RNA HOST2对胰腺癌细胞增殖迁移和侵袭的影响

目的:探讨长链非编码RNA(lncRNA)HOST2对胰腺癌细胞增殖、迁移和侵袭的影响及机制。方法:qRT-PCR检测正常胰腺上皮细胞系HPDE6-C7及胰腺癌细胞系Panc-1、AsPC-1、BxPC-3、HPAC中lncRNAHOST2表达水平。将Panc-1细胞分别转染siRNA-HOST2(si-HOST2组)和阴性对照序列(阴性对照组)后,用MTT法测定细胞增殖,细胞划痕和Transwell实验测定细胞迁移和侵袭,Westernblot测定上皮-间质转化(EMT)相关蛋白vimentin、Snail、Twist的表达。以无转染的Panc-1细胞为空白对照组。结果:与正常胰腺上皮细胞HPDE6-C7相比,lncRNAHOST2在各胰腺癌细胞系中的表达均明显上调(均P0.05)。与空白对照组比较,si-HOST2组细胞增殖、迁移和侵袭能力均明显减弱,vimentin、Twist1、Snail蛋白相对表达量均明显下调(均P0.05),而阴性对照组上述指标均无明显变化(均P0.05)。结论:lncRNAHOST2在胰腺癌细胞中高表达,且与胰腺癌增殖、迁移和侵袭密切相关,其机制可能与调节EMT相关蛋白的表达有关。     

叉头框蛋白O3在胰腺癌中的表达及其对胰腺癌细胞的影响

目的分析叉头框蛋白O3(FOXO3)在胰腺癌中的表达及其对胰腺癌细胞运动和增殖的影响。方法检索LinkedOmics数据库胰腺癌患者胰腺癌和癌旁组织FOXO3表达。Western印迹和实时定量聚合酶链反应检测胰腺癌细胞系和人胰腺星状细胞HPSC中FOXO3表达。选择低表达FOXO3的PANC-1、MIAPaCa-2胰腺癌细胞, 分别转染FOXO3过表达质粒和阴性对照质粒。克隆形成实验、细胞划痕实验、Transwell侵袭实验和细胞周期检测各组胰腺癌细胞运动和增殖能力。结果 LinkedOmics数据库中, 64例胰腺癌患者癌组织中FOXO3蛋白相对表达水平明显低于癌旁组织(t=8.36, P<0.001)。PANC-1细胞过表达FOXO3后细胞克隆数为(30.0±6.6)个(40倍视野下计数), 低于阴性对照细胞的(92.7±6.7)个, 差异有统计学意义(t=11.54, P<0.001)。PANC-1和MIAPaCa-2在上调FOXO3表达后细胞划痕修复率较对照组显著下降。Transwell实验PANC-1细胞FOXO3过表达后(每个100倍视野下)穿膜数(21.0±6...     

胰腺星状细胞对胰腺癌细胞增殖能力的影响及机制

目的 观察胰腺星状细胞(PSC)对人胰腺癌细胞株增殖能力的影响,探讨其分子机制.方法 用免疫印迹实验检测成纤维细胞生长因子(FGFs)在胰腺癌细胞及PSC中的表达及分泌;噻唑蓝(MTT)比色法检测PSC细胞条件培养基(CDM)对胰腺癌细胞体外增殖的影响,以及除去FGFs之后影响的变化;MTT法检测PSC细胞CDM对Cyclopamine抑制胰腺癌细胞增殖作用的影响;体内实验观察PSC对胰腺癌细胞成瘤能力的影响.结果 PSC主要表达并分泌FGF2,而胰腺癌MIA PaCa-2和PANC-1细胞则主要表达FGF5;PSC细胞CDM刺激48 h后,胰腺癌MIA PaCa-2和PANC-1细胞体外增殖能力分别为对照组的(1.2993±0.1170)倍和(1.2447±0.0123)倍(P＜0.05);中和CDM中FGFs后,FGFs(-)CDM对胰腺癌细胞增殖的刺激作用显著削弱;与单纯注射胰腺癌PANC-1细胞的裸鼠皮下种植瘤比较,PSC与PANC-1细胞混合注射组的平均肿瘤体积、质量均明显增加,分别由380.13 mm3和170 g增加至601.31 mm3和349 g(P＜0.05);PSC细胞CDM处理后,Cyclopamine对胰腺癌MIA PaCa-2和PANC-1细胞的增殖抑制作用显著下降(P＜0.01).结论 PSC在体内、体外均显著刺激胰腺癌细胞的增殖,增强其成瘤能力,其机制与PSC旁分泌FGF2作用于癌细胞相关;PSC显著降低了胰腺癌细胞对Hedgehog信号通路特异性抑制剂Cyclopamine治疗的敏感性.

Abstract：

Objective To assess the effects of pancreatic stellate cells (PSC) on proliferation of pancreatic cancer cells and to reveal its possible mechanism. Methods Expression and secretion of fibroblast growth factor (FGF) ligands in both pancreatic cancer cells and stellate cells were determined by immunoblotting analysis. Mmethyl thiazol tetrazolium (MTT) assay was used to examine the effects of conditioned medium (CDM) of PSC on the proliferation of pancreatic cancer cells. An in vivo tumorigenicity assay was used to evaluate the effect of PSC on xenograft formation in cancer cells. Results FGF2 was predominantly expressed and secreted by PSC. Yet MIA PaCa-2 and PANC-1 pancreatic cancer cells mainly expressed FGF5. CDM of PSC enhanced the proliferation of MIA PaCa-2 and PANC-1 cells for ( 1. 2993 ±0. 1170 ,P ＜0. 05 ) times and ( 1. 2447 ±0. 0123 ,P ＜0. 05 ) times, respectively. Neutralizing the effects of FGFs in the CDM by heparin-sepharose precipitation abolished this effect. The volume and weight of subcutaneous tumors in nude mice by injection of combination of pancreatic cancer cells with PSC were significantly greater than those by injection of PANC-1 cells alone (380. 13 mm3 and 170 g versus 601.31 mm3and 349 g,P ＜0. 05, respectively). The CDM of PSC reduced the antiproliferative effect by cyclopamine on pancreatic cancer cells ( P ＜ 0. 01, respectively). Conclusion We identified in this study a mechanism based on stroma-tumor interactions involving PSC that can contribute to enhance the proliferation of human pancreatic cancer cells.     

miR-519d在胰腺癌细胞中的表达及其作用

目的:探讨miR-519d在胰腺癌细胞中的表达及作用。方法:用qRT-PCR检测miR-519d在胰腺癌细胞系AsPC-1、BxPC-3、Capan-2、Panc-1及正常胰腺导管上皮细胞系HPDE6-C7中的表达。将Panc-1细胞分别转染miR-519d过表达质粒(miR-519d组)与阴性对照质粒(阴性对照组),以无处理的Panc-1细胞为空白对照组,用MTT法、Transwell实验、Western blot分别检测转染后细胞的增殖和侵袭能力、凋亡情况以及X连锁凋亡抑制蛋白(XIAP)的表达。结果:各胰腺癌细胞系中miR-519d相对表达量均明显低于正常胰腺导管上皮细胞系HPDE6-C7(均P0.05);与空白对照组比较,miR-519d组细胞增殖能力降低(培养72 h后明显降低)、凋亡率明显升高、侵袭能力明显减弱、XIAP蛋白表达量明显降低(均P0.05);阴性对照组各项指标与空白对照组差异均无统计学意义(均P0.05)。结论:miR-519d在胰腺癌细胞中表达下调,miR-519d表达下调有增强胰腺癌细胞增殖和侵袭能力、降低凋亡的作用,该作用可能与其调节XIAP蛋白的表达有关。     

人胰腺癌细胞系MIA PaCa-Ⅱ神经侵袭原位移植瘤动物模型的建立

目的 建立人胰腺癌细胞系MIA PaCa-Ⅱ裸鼠胰腺原位移植瘤模型并观察神经侵袭情况,为研究胰腺癌神经侵袭的发生、发展提供实验依据和条件.方法 将人胰腺癌细胞系MIA PaCa-Ⅱ行裸鼠背部皮下接种.建立高转移特性胰腺癌裸鼠皮下移植瘤模型,然后将高转移性移植瘤组织接种于裸鼠胰腺被膜下,分别于4周、6周和8周处死裸鼠行移植瘤组织解剖和病理学检查.测量移植瘤大小和重量,并用HE和银染方法观察神经侵袭情况.结果 模型建立过程中,胰腺癌细胞系MIA PaCa-Ⅱ细胞裸鼠皮下接种成瘤率为100%(10/10),皮下移植瘤呈局限性生长,无脏器和神经转移.原位移植4周、6周和8周后,胰腺癌原位移植瘤成瘤率均为100%(10/10),神经转移率分别为50%(5/10)、80%(8/10)和60%(6/10),并可见多个脏器转移,以肝脏、肝门淋巴结、胃窦转移和腹膜播散多见.结论 成功建立了人胰腺癌细胞系MIA PaCa-Ⅱ裸鼠胰腺原位移植瘤模型并观察了神经侵袭情况,此模型为一较理想的"拟人"神经浸润转移模型,可用于胰腺癌体内嗜神经性机制的研究.     

微小RNA-618通过靶向羧基末端结合蛋白2抑制胰腺癌细胞增殖、侵袭和迁移

目的:探讨微小RNA(miR)-618及羧基末端结合蛋白2(CtBP2)对胰腺癌增殖、侵袭和迁移的影响及其作用机制。方法:采用实时定量反转录聚合酶链反应(RT-qPCR)检测胰腺癌细胞中miR-618的表达;分别转染miR-618 inhibitor和mimics后,采用细胞计数试剂盒(CCK-8)、克隆集落形成及Tr...     

POLE2对非小细胞肺癌细胞侵袭迁移能力的影响

目的 探讨POLE2对非小细胞肺癌（NSCLC）细胞侵袭迁移能力的影响。方法 采用实时荧光定量PCR（qRT-PCR）检测人支气管上皮样细胞BEAS-2B和NSCLC细胞A549、SPC-A1中POLE2的表达水平。构建POLE2过表达细胞模型,qRT-PCR和蛋白质印迹法（Western blot）验证转染效率。采用Cell Counting Kit-8（CCK-8）实验检测NSCLC细胞的增殖能力,Transwell实验检测NSCLC细胞的侵袭迁移能力,qRT-PCR检测MMP9的表达水平。结果 人NSCLC细胞SPC-A1、A549中POLE2的表达水平显著高于人支气管上皮样细胞BEAS-2B（P<0.05）。过表达POLE2促进了A549细胞的增殖和侵袭迁移,上调了MMP9的表达（P<0.05）。结论 过表达POLE2可能通过上调MMP9促进NSCLC细胞的侵袭迁移。     

MAPK13调控胆管癌细胞增殖、侵袭和上皮间质转化进程的机制研究

目的 本研究旨在分析丝裂原活化蛋白激酶13(MAPK13)在胆管癌组织及细胞中的表达水平并探讨其在胆管癌细胞增殖、侵袭和上皮间质转化(EMT)中的作用。方法 通过微阵列分析筛选胆管癌组织中差异表达的mRNA,通过实时荧光定量PCR(qRT-PCR)、蛋白印迹及免疫组化染色验证MAPK13在肿瘤组织和细胞中的表达情况。进一步通过细胞转染构建MAPK13敲低(si-MAPK13)后,通过细胞活力实验检测胆管癌细胞增殖能力,流式细胞仪检测细胞凋亡,Transwell法检测细胞的迁移和侵袭性。最后,通过裸鼠成瘤实验检测MAPK13对体内成瘤及相关蛋白表达的影响。结果 本研究通过微阵列分析发现MAPK13在肿瘤组织中的表达存在显著差异,进一步通过qRT-PCR、蛋白印迹和免疫组化染色分析发现,与癌旁组织比较,MAPK13在mRNA和蛋白质水平的表达情况在肿瘤组织及细胞中均显著升高且差异具有统计学意义(t=27.92,6.90;均P<0.01)。进一步细胞活力检测表明,抑制MAPK13的表达后细胞增殖数量明显减少(F=32.13,P<0.01)。Transwell实验则显示细胞迁移和侵...     

肿瘤相关巨噬细胞通过PI3K/Akt途径促进胰腺癌浸润迁移的研究

目的研究PI3K/Akt信号通路对胰腺癌细胞PANC-1浸润迁移能力的影响,进一步探讨肿瘤相关巨噬细胞促进胰腺癌发生发展的分子机制。 方法通过密度梯度离心法从健康成人外周血中分离单个核细胞,用IL-4体外诱导选择性激活的巨噬细胞(M2)。采用实时荧光定量PCR和Western blotting法检测胰腺癌PANC-1细胞PI3K、Akt mRNA和蛋白表达水平的变化,利用Transwell侵袭实验与划痕实验观察细胞浸润迁移能力的变化。 结果体外模拟胰腺癌微环境,将胰腺癌PANC-1细胞与不同激活状态的巨噬细胞共培养,证明M2可显著上调胰腺癌PANC-1细胞PI3K、Akt的mRNA和蛋白水平,共培养20 h后可明显促进胰腺癌PANC-1细胞的浸润与迁移能力。 结论肿瘤相关巨噬细胞可通过PI3K/Akt信号通路促进胰腺癌细胞的浸润与迁移。     

沉默前列腺特异性膜抗原促进前列腺癌LNCAP细胞上皮-间质转化及迁移、侵袭的研究

目的 利用RNAi技术沉默LNCAP细胞中前列腺特异性膜抗原（PSMA）表达并检测表达情况,检测沉默PSMA后LNCAP细胞迁移及侵袭等生物学行为的变化情况,以及LNCAP细胞中上皮-间质转化标志蛋白的变化情况。方法 培养LNCAP细胞,分为si-PSMA组,阴性对照（negative control siRNA）组,抑制剂LY294002组和LY294002+si-PSMA组,采用qRT-PCR和Western blot技术检测沉默PSMA后LNCAP细胞中PSMA的mRNA和蛋白表达情况,通过Transwell小室穿透实验检测LNCAP细胞迁移及侵袭能力改变,通过Western blot蛋白印迹法检测E-cadherin、β-cadherin、vimentin,snail等细胞上皮-间质转化标志蛋白的表达情况以及p-Akt(ser473)蛋白表达情况。结果 与阴性对照组相比,si-PSMA组PSMA的mRNA和蛋白表达水平都明显降低（P<0.05）,Transwell结果显示迁移及侵袭细胞增多（P<0.01）,LY294002组细胞迁移及侵袭下调（P<0.05）,...     

Specific gene expression and therapy for pancreatic cancer using the cytosine deaminase gene directed by the rat insulin promoter

Suicide gene therapy has been shown to be an effective means of destroying pancreatic cancer cells, but cell-specific delivery of the gene is required to limit host toxicity. The objective of this study is to determine whether the rat insulin promoter (RIP) will permit cell-specific gene delivery and subsequent cell death in human pancreatic cancer cells. The RIP DNA was amplified using polymerase chain reaction (PCR), and the purified fragment was inserted into pCR-Blunt II-TOPO plasmid at the SpeI site, which contains the coding sequence of yeast cytosine deaminase (CD). Transfection assays were carried out using both RIP-lacZ and RIP-CD DNA constructs in two human pancreatic cancer cell lines, PANC-1 and MIA PaCa-2. Reporter assays using X-gal staining were performed, and the in vitro cytotoxicity was examined in RIP-CD-transfected cells treated with 5-.ucytosine for 5 days. The expression levels of CD protein in the transfected cells were determined 2 days after transfection by Western blot analysis. The expression levels of insulin promoter factor (IPF-1/PDX-1) in these human pancreatic cell lines, as well as in freshly isolated human pancreatic cancer specimens, were determined using in situ immunohistochemistry analysis. After transfection with RIP-lacZ, only PANC-1 cells, but not MIA PaCa-2 cells, were positive for RIP-lacZ expression, indicating that RIP-directed reporter gene expression occurred only in PANC-1 cells. After transfection with RIP-CD and treatment with 5-flucytosine, PANC-1 cells had a significantly increased cell death rate compared with that of MIA PaCa-2 cells, suggesting that RIP-directed suicide gene expression occurred only in PANC-1 cells. Western blot analysis demonstrated that only PANC-1 cells were able to express the CD protein and that significantly increased levels of PDX-1 were found in PANC-1 but not in Mia PaCa-2 cells. In situ immunohistochemical analysis of both cell lines showed that PDX-1 was only expressed in the nuclei of PANC-1 cells and not in MIA PaCa-2 cells. Furthermore, two freshly isolated human pancreatic cancer specimens had significantly increased levels of PDX-1. The RIP is activated in PANC-1 cells, but not in Mia PaCa-2 cells, and the mechanism of activation is via PDX-1. Pancreatic cancer-specific cytotoxicity can be achieved with the use of RIP-CD and 5-flucytosine treatment in vitro. Significantly increased levels of PDX-1 have been found in human pancreatic cancer specimens. These results suggest that RIP could be used for cell-specific suicide gene therapy to target human pancreatic tumors. Presented at the Forty-Fourth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Florida May 18–21, 2003 (oral presentation). Supported by an Advances in Technology Transfer Grant (ATP1176) from the State of Texas Department of Education and by grant NCI R01 (CA95731).     

分选蛋白17对胰腺癌细胞生物学性状的影响

目的:探讨分选蛋白(SNX)17通过激活表皮生长因子受体(EGFR)影响胰腺癌细胞侵袭、增殖和迁移能力。方法:采集3例人胰腺癌组织及癌旁组织样本,自2021年1月至2021年3月收集于贵州医科大学附属医院肝胆外科,用免疫组织化学(IHC)染色检测癌组织与癌旁组织中SNX17的表达量。用实时定量反转录聚合酶链反应(RT-...     

The cytotoxic effects of bile acids in crude bile on human pancreatic cancer cell lines

Pancreatic cancer frequently causes extrahepatic cholestasis. To identify the direct effects of bile acids in jaundiced serum on pancreatic cancer, the proliferation of PANC-1 and MIA PaCa-2 cells as well as the ultrastructural alteration of PANC-1 cells cultured in crude bile modified media were studied. The growth of these cells in the RPMI-1640 media with or without 1%, 2%, and 4% of the refined crude bile was assessed after 48 and 96 h of incubation. The ultrastructure of PANC-1 cells was investigated by scanning and transmission electron microscopy after 24 and 48 h of incubation. The proliferation of both cell lines in the bile-treated media was greatly inhibited. The inhibitory rates of bile on PANC-1 ranged from 24.1% ± 3.3% to 66.9% ± 6.6% (P < 0.01) and those on MIA PaCa-2 ranged from 16.7% ± 3.8% to 50.7% ± 5.5%. (P < 0.01). When the bile-added media were replaced, the cells were able to restore their proliferating ability. The PANC-1 cells incubated in the bile-supplied media indicated that the mirovilli, mitochondria, and other organelles had thus been injured. These results suggest that bile acids appear to inhibit the proliferation of PANC-1 and MIA PaCa-2 cells, and the probable inhibitory mechanism is mainly considered to be due to the cytotoxicity of such bile acids. Received: November 2, 1999 / Accepted: May 30, 2000