高迁移率族蛋白B-1与胃肠道肿瘤的相关性

高迁移率族蛋白B-1(HMGBl)是一种非组蛋白DNA结合蛋白和细胞外损伤相关模式分子,在正常情况下定位于细胞内,发挥多种生物学效应.研究证实,几乎所有的胃肠道肿瘤都有HMGBI的表达,且HMGBI表达与胃肠道肿瘤的生长、增殖、浸润和转移密切相关.研究还发现HMGB1抑制剂可抑制胃肠道肿瘤的生长和转移,有望成为胃肠道肿...     

高迁移率族蛋白框1反义核酸抑制人胰腺癌细胞系PCNA-1侵袭的研究

背景与目的:研究证明高迁移率族蛋白框1(highmobilitygroupbox1,HMGB1)在大多数未成熟及恶性肿瘤细胞中高表达,它与细胞增殖、侵袭、转移有密切关系。我们前期的研究证明HMGB1在胰腺癌组织中高表达并与肿瘤的侵袭及转移显著性相关。本研究的目的是观察HMGB1反义核酸对胰腺癌PCNA-1细胞体外侵袭能力的影响,并探讨其作用机制。方法:以脂质体介导方法将HMGB1反义表达载体转染胰腺癌细胞株PCNA-1,采用逆转录-聚合酶链反应(RT-PCR)方法检测HMGB1、基质金属蛋白酶(matrixmetalloproteinase-2,-9,MMP-2,MMP-9)mRNA的表达,Westernblot法检测HMGB1蛋白表达,明胶酶谱法(gelatinzymography)检测MMP-2和MMP-9活性的变化,Boyden小室法检测PCNA-1的体外侵袭能力。结果:HMGB1反义核酸明显抑制PCNA-1细胞HMGB1mRNA和蛋白的表达。转染后,MMP-2及MMP-9mRNA表达和酶活性亦受到显著抑制(P<0.01)。另外,HMGB1反义核酸的导入显著减弱了胰腺癌细胞的跨膜侵袭能力(P<0.01)。结论:HMGB1在胰腺癌侵袭转移中,阻断HMGB1基因的表达,可能是阻抑胰腺癌转移的一种新策略。     

高迁移率族蛋白B1与肿瘤侵袭性的研究进展

既往高迁移率族蛋白B1被认为是典型的非组DNA结合蛋白,在细胞核内参与DNA的稳定及基因转录的功能。近年来研究表明,高迁移率族蛋白B1在多种肿瘤内过度表达并且与肿瘤的浸润性生长密切相关。     

高迁移率族蛋白A1与白血病

 高迁移率族蛋白A1（HMGA1）属于高迁移率蛋白家族（HMG）,在人体中分布广泛,参与多种生理病理过程。研究发现其在多种肿瘤,包括在白血病中高表达,以癌基因形式参与了肿瘤的发病。文章对HMGA1在白血病发病中的意义进行综述。     

高迁移率族蛋白A1在肿瘤中的作用及其机制

高迁移率族蛋白A1 (HMGA1)是非组蛋白染色质蛋白超家族的成员,广泛存在于真核生物细胞核中,主要参与对基因表达转录的调控.研究表明几乎所有的人类恶性肿瘤中都有HMGA1异常表达,其在癌症的发生发展中可能有重要作用,但具体致癌机制尚未完全清楚.构建的HMGA1转染系统在以后的肿瘤研究中将有潜在的应用价值,也为肿瘤的治...     

高迁移率族蛋白1基因在胰腺癌组织中的表达及其临床意义

目的　探讨胰腺癌组织中高迁移率族蛋白 1(HMGB1)蛋白表达情况及其与肿瘤分化程度、大小、浸润和转移的关系。方法　采用免疫组化SABC方法 ,检测 73例胰腺癌组织、10例癌旁组织、6例正常胰腺组织中HMGB1蛋白表达情况。结果　HMGB1在胰腺癌组织中呈强阳性表达 ( 76.7% ) ,在癌旁组织中仅呈微弱表达 ,正常胰腺组织中无表达 ;HMGB1阳性率与肿瘤分化程度无关 (P >0 .0 5 ) ;与肿瘤的大小、浸润及转移呈正相关 (P <0 .0 1)。结论　HMGB1在胰腺癌组织中呈强阳性表达 ,可作为胰腺癌浸润、转移及预后的重要判定指标之一     

胰腺癌组织中高迁移率族蛋白1和基质金属蛋白酶2的表达研究

目的:研究胰腺癌组织中高迁移率族蛋白1 ( high mobility group box 1,HMGB1)及基质金属蛋白酶2 ( matrixmetalloproteinase 2, MMP 2)蛋白表达并探讨其与癌分化程度、肿瘤大小、浸润、淋巴及血道转移的关系。方法:用免疫组织化学SP 方法,检测73 例胰腺癌组织、30例癌旁组织HMGB1 及MMP -2 蛋白表达。结果:HMGB1和MMP 2在胰腺癌中的阳性表达率分别为76. 7% ( 56/73 )和64 4% ( 47/73 ),在癌旁组织中分别为20 .0%(6/30)和23 3%(7/30), 两者在癌组织与癌旁组织间表达差异均有统计学意义,P<0. 01。HMGB1 和MMP- 2 的阳性率与癌分化程度无关,P>0 .05;与肿瘤的大小、浸润、淋巴及血道转移呈正相关,P<0 .05或<0 .01;HMGB1 和MMP -2 在胰腺癌组织中表达呈正相关,P< 0. 01。结论:HMGB1 和MMP- 2 在胰腺癌生长、侵袭和转移过程中起着重要的作用, 联合检测有利于评估胰腺癌的生物学行为和判     

let-7与高迁移率族蛋白A在肿瘤中的研究进展

高迁移率族蛋白A(HMGA)在多种肿瘤的发生发展中起着重要的作用,其表达水平会随肿瘤恶性程度的增高或转移潜能的增大而异常增高.let-7是一类内源性非编码的微小RNA,可作为肿瘤抑制因子对HMGA基因进行负性调控.在对多种肿瘤的研究中已经观察到let-7表达水平的下降,并伴随HMGA表达水平的上升,这对肿瘤的早期诊断提...     

高迁移率族蛋白B1与胰腺癌的关系

高迁移率族蛋白B1(HMGB1)是细胞内的非组蛋白染色体结合蛋白,在维持核小体稳定和DNA重组、复制、修复及基因转录中发挥着重要作用.而细胞外HMGB1可作为一种"晚期炎症介质",在炎症的晚期阶段启动着炎症反应.最近研究发现,HMGB1作为一种非组蛋白染色体蛋白质,与胰腺癌的生长、浸润、转移密切相关,能促使细胞外基质降解,促进胰腺癌浸润、转移.     

Doxycycline induces caspase-dependent apoptosis in human pancreatic cancer cells

Doxycycline (DC) belongs to the tetracycline family of antibiotics and has been used clinically for over 5 decades. Despite advances in understanding the molecular pathogenesis of pancreatic cancer, no chemotherapy course has shown significant effectiveness. Hence new treatments are needed. In this study we report the pro-apoptotic effects of DC in 2 pancreatic adenocarcinoma cell lines, T3M4 and GER. Cell proliferation was measured using the SRB protein dye. Induction of apoptosis was detected using ELISA. Caspase activation was detected using either immunoblotting or a colorimetric assay based on cleavage of caspase-associated substrates. Expression of proteins and post-translational modifications were determined using immunoblotting. Treatment of pancreatic cancer cells with DC reduces their proliferation. This reduction is, at least partly, due to increased caspase-dependent apoptosis involving activation of caspase3, caspase7, caspase8, caspase9, caspase10 and increased levels of FADD. Inhibition of caspase8 or caspase10 but not caspase9 significantly decreases DC-induced apoptosis in both cell lines. Furthermore treatment of pancreatic cancer cells with DC increases protein levels of Bax and phosphorylation of members of the p38MAPK pathway such as p38MAPK, MKK3/6 and MAPKAPK2. These results provide an insight into mechanisms behind the pro-apoptotic effects of DC in pancreatic cancer cells.     

Parthenolide induces proliferation inhibition and apoptosis of pancreatic cancer cells in vitro

Background

To explore the anti-tumor effects of parthenolide in human pancreatic cancer.

Methods

BxPC-3 cell, a human pancreatic cancer, was treated with parthenolide at different concentrations. The MTT assay was used to analyze cell viability. Flow cytometry and DNA fragmentation analysis were applied to evaluate apoptosis after parthenolide treatment. The wound closure and cell invasion assay were also employed in the study. Western blotting was used to demonstrate Bad, Bcl-2, Bax, caspase-9 and pro-caspase-3 expression.

Results

The MTT assay indicated that the pancreatic cancer growth could be dose-dependently inhibited by parthenoolide. This phenomenon was confirmed by flow cytometry and DNA fragmentation analysis. The wound closure assay and cell invasion assay showed that BxPC-3 cell was significantly suppressed by parthenolide at 7.5 μM and 15 μM. Western Blotting demonstrated the Bcl-2 and pro-caspase-3 were down-regulated while the Bax and caspase-9 were up-regulated. No alteration in Bad expression was found after treatment.

Conclusions

The parthenolide can inhibit the cell growth, migration, and induce the apoptosis in human pancreatic cancer. These findings may provide a novel approach for pancreatic cancer treatment.     

二甲双胍对人胰腺癌细胞增殖与凋亡的影响

背景与目的:近年研究发现二甲双胍对多种肿瘤具有抑制作用,部分临床研究也发现二甲双胍可以降低糖尿病并发胰腺癌的风险和降低胰腺癌的死亡危险。本研究从细胞水平着手研究二甲双胍对胰腺癌细胞增殖和凋亡的影响,并初步探讨其可能机制。方法:体外培养人胰腺癌细胞株Bxpc-3,予二甲双胍进行干预作为二甲双胍干预组,无药物组作为对照组。以MTT检测二甲双胍对Bxpc-3细胞存活率的影响,流式细胞术检测二甲双胍对Bxpc-3细胞周期的影响,流式细胞术及Hoechst 33258荧光染色法检测细胞凋亡,RT-PCR检测AMPKα1、Bax、Bcl-2、Caspase-3、Cyclin D1 mRNA的表达。蛋白质印迹法(Western blot)检测Cyclin D1、Bax、Bcl-2、Caspase-3蛋白的表达。结果:与对照组相比,MTT检测结果显示,二甲双胍可以抑制人胰腺癌细胞株Bxpc-3的增殖,并呈时间-浓度依赖性(F=8.99、124和114.61,P<0.01);流式细胞术检测结果显示,二甲双胍干预组与对照组相比,G0/G1期细胞所占百分比增加(t=-8.71,P<0.01),S期(t=7.54,P<0.01)及G2/M期(t=7.00,P<0.01)细胞所占百分比减少;流式细胞术(早期凋亡率t=-2.68,晚期凋亡率t=1.29,总凋亡率t=-0.85)及Hoechst 33258荧光染色法(t=-0.46)结果显示,两组细胞凋亡率差异无统计学意义(P>0.05);RT-PCR结果显示,二甲双胍干预组Cyclin D1 mRNA表达明显降低(t=4.96,P<0.01),AMPKα1、Bax、Bcl-2、Caspase-3 mRNA表达与对照组相比,差异无统计学意义(t=1.68、-0.56、-1.80、0.67,P>0.05);Westernblot结果显示,二甲双胍干预组Cyclin D1蛋白表达明显降低(t=7.02,P<0.01),Bax、Bcl-2、Caspase-3蛋白表达与对照组相比,差异无统计学意义(t=-0.11、-0.20,0.11,P>0.05)。结论:二甲双胍能显著抑制人胰腺癌细胞株Bxpc-3的增殖,机制主要与其阻滞细胞周期、下调Cyclin D1表达有关;二甲双胍对Bxpc-3细胞的凋亡无明显诱导作用。     

激活和抑制Stat 3信号途径对胰腺癌细胞侵袭能力的影响

目的:通过激活和阻断人胰腺癌细胞中的Stat3信号转导通路,观察细胞株侵袭能力的变化并探讨其作用机制.方法:采用IL-6处理人胰腺癌细胞Capan-2,AG490处理人胰腺癌细胞SW1990后,MTT法检测细胞的增殖状态,免疫细胞化学法和Western 印迹法检测p-Stat3的表达,实时荧光定量PCR(real-time fluorogentic quantitative PCR, RFQ-PCR)和Western 印迹法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶-2(matrix metalloproteinase 2,MMP-2) mRNA及其蛋白的表达,体外侵袭实验检测细胞的侵袭能力.结果:IL-6可促进Capan-2细胞的增殖能力提高(P<0.05),p-Stat3的表达增强,VEGF和MMP-2 mRNA和蛋白表达明显升高(P<0.05),细胞侵袭能力增强.AG490可抑制SW1990细胞株的增殖(P<0.05),p-Stat3的表达下降,VEGF和MMP-2 mRNA和蛋白表达明显下降(P<0.05),侵袭能力减弱.结论:Stat3信号转导通路在胰腺癌侵袭过程中起着重要作用,以Stat3信号转导通路为靶点的基因治疗可能为胰腺癌治疗提供新的方向.     

12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells

Arachidonic acid release from membrane phospholipids is essential for tumour cell proliferation. Lipoxygenases constitute a pathway for arachidonate metabolism. The present study investigated the expression of 12-lipoxygenase and its effect on cell proliferation as well as survival in two human gastric cancer cell lines (AGS and MKN-28). RT-PCR and western blots, respectively, showed 12-LOX mRNA and protein expression in both AGS and MKN-28 cell lines. Treatment with a 12-LOX inhibitor, baicalein, significantly inhibited cancer cell proliferation, but a metabolite of 12-LOX activity, 12 hydroxyeicosatetraenoic acid (12-HETE) reversed baicalein-induced growth inhibition. Furthermore, the blockade of the 12-LOX pathway through a 12-LOX inhibitor and antisense induced apoptosis of gastric cancer cell lines. The biochemical characteristics of apoptosis were p53-independent combined with a decrease in bcl-2 expression. Caspase-7 was proteolytically activated and responsible for the apoptosis execution.