δ-生育三烯酚诱导人肝癌HepG2细胞凋亡的机制研究

目的:探讨δ-生育三烯酚诱导人肝癌HepG2细胞凋亡的作用机制.方法:应用MTT法检测δ-生育三烯酚对人肝癌HepG2细胞增殖的影响,应用高内涵活细胞成像系统检测δ-生育三烯酚对人肝癌HepG2细胞凋亡率、细胞周期以及线粒体膜电位的影响,Western印迹法检测δ-生育三烯酚对人肝癌HepG2细胞凋亡相关蛋白(如caspase-3、caspase-8、caspase-9、Bcl-2、Bax、tBid和cytochrome C)表达的影响.结果:δ-生育三烯酚呈浓度依赖性地抑制肝癌HepG2细胞生长并诱导其凋亡,其机制为δ-生育三烯酚降低线粒体膜电位,并诱导cytochrome C从线粒体释放到细胞质中,调控Bcl-2家族蛋白表达(如上调Bax及tBid蛋白的表达,下调Bcl-2蛋白的表达),继而引起caspase-3、caspase-8和caspase-9的活化,最终导致肝癌 HepG2细胞凋亡.结论:δ-生育三烯酚可能通过线粒体途径及膜死亡受体途径共同诱导人肝癌细胞 HepG2凋亡.     

γ-生育三烯酚对人胃癌 SGC-7901细胞的抑制作用及机制

目的 探讨γ -生育三烯酚(γ -tocotrienol)对人胃癌细胞SGC-7901抑制作用.方法 采用离体细胞培养技术,利用细胞生长曲线,单细胞凝胶电泳、琼脂糖凝胶电泳、透射电镜技术等方法,观察 γ-生育三烯酚对SGC-7901细胞生长抑制及其肿瘤细胞的损伤作用.结果 γ -生育三烯酚可明显抑制SGC-7901细胞增殖,抑制作用随作用浓度增加、作用时间延长而增强;并能引起人胃癌细胞株SGC-7901细胞DNA 分子的损伤以及细胞超微结构变化,如线粒体损伤和形成凋亡小体,且与γ-生育三烯酚作用的浓度存在一定的相关性.结论 γ -生育三烯酚对SGC-7901细胞生长有明显抑制作用,其抑制机制与参与DNA损伤、诱导细胞凋亡有关.     

γ-生育三烯酚对人胃癌SGC-7901细胞的抑制作用及机制

目的：探讨γ-生育三烯酚（γ-tocotrienol）对人胃癌细胞SGC-7901抑制作用。方法：采用离体细胞培养技术,利用细胞生长曲线,单细胞凝胶电泳、琼脂糖凝胶电泳、透射电镜技术等方法,观察γ-生育三烯酚对SGC-7901细胞生长抑制及其肿瘤细胞的损伤作用。结果：γ-生育三烯酚可明显抑制SGC-7901细胞增殖,抑制作用随作用浓度增加、作用时间延长而增强;并能引起人胃癌细胞株SGC-7901细胞DNA分子的损伤以及细胞超微结构变化,如线粒体损伤和形成凋亡小体,且与γ-生育三烯酚作用的浓度存在一定的相关性。结论：γ-生育三烯酚对SGC-7901细胞生长有明显抑制作用,其抑制机制与参与DNA损伤、诱导细胞凋亡有关。     

生育三烯酚抗肿瘤作用研究进展

生育三烯酚属于维生素E家族,在体内外均具有抗肿瘤作用,主要通过抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡、抗血管生成以及调节相关信号转导途径来实现.本文就生育三烯酚的抗肿瘤作用及其机制作一综述,以了解其生物学功能.     

生育三烯酚增敏化疗药物抗肿瘤作用机制的研究进展

恶性肿瘤存在多药耐药,严重影响治疗效果.因此预防肿瘤产生多药耐药已成为肿瘤药物学研究的主要问题之一.近年来文献报道,生育三烯酚作为化疗药物的增敏剂,不论是在体外实验还是动物实验中都展现出协同抗肿瘤效应.本文就生育三烯酚的协同抗肿瘤机制作一综述,为以后生育三烯酚作为化疗药物的增敏剂应用于临床提供更多证据.     

棉籽酚诱导结肠癌细胞系凋亡的作用

目的：研究棉籽酚ｇｏｓｓｙｐｏｌ对结肠癌细胞的致凋亡作用及其方式。方法：将不同浓度棉籽酚与结肠癌细胞株ＨＴ２９和Ｌｏｖｏ作用,采用集落形成法检测细胞经棉籽酚处理后的细胞存活曲线,通过荧光显微镜观察用药后细胞周期时相改变。结果：ＨＴ２９和Ｌｏｖｏ经棉籽酚处理后增殖能力降低,２种细胞均显示明显凋亡征象,表现典型ＤＮＡ梯,２种细胞均于用药后２４与４８ｈ出现凋亡峰（亚Ｇ１峰）,并随药物浓度和用药时间增加而     

β-榄香烯联合三苯氧胺抑制乳腺癌MCF-7细胞生长的实验研究

目的:研究β-榄香烯联合三苯氧胺对乳腺癌MCF-7细胞生长有无协同抑制作用,并探讨其可能的机制.方法: 采用MTT法检测β-榄香烯联合三苯氧胺对MCF-7细胞的增殖抑制作用,流式细胞仪测定细胞周期和凋亡率,免疫组化SP法检测bcl-2、pS2表达变化.结果: 不同剂量的β-榄香烯联合治疗剂量的三苯氧胺,吸光度均值较单用三苯氧胺明显下降,相应 的细胞抑 制作用明显上升;流式细胞仪检测G0/G1期细胞比例增加,用药后凋亡率升高,bcl-2、pS2在联合用药后表达明显下调.结论:β-榄香烯使三苯氧胺对乳腺癌MCF-7细胞的抑制作用显著增强,提示榄香烯与三苯氧胺具有协同增效作用,其作用机制与影响细胞周期进程,协同促进凋亡,下调bcl-2、pS2表达有关.     

和厚朴酚对人皮肤鳞癌细胞A431增殖凋亡作用及可能的机制分析

目的:研究和厚朴酚（Honokial,HNK）对人皮肤鳞癌细胞A431增殖凋亡作用及可能的机制分析。方法:采用CCK8实验方法检测和厚朴酚对A431细胞增殖的影响;Western blot定量分析和厚朴酚对Bcl-2和Bad蛋白表达的影响;Western blot定分析和厚朴酚对A431细胞中p53蛋白表达的影响;利用p53过表达腺病毒,并联合应用药物,通过CCK8和Western blot方法分析和厚朴酚对细胞增殖和凋亡的影响。结果:和厚朴酚以浓度和时间依赖性地抑制A431细胞增殖,并诱导其凋亡,上升Bad蛋白水平,下调Bcl-2蛋白水平;和厚朴酚可上调A431细胞中p53蛋白表达水平;加入p53过表达腺病毒可增强和厚朴酚的作用,抑制细胞增殖,促进细胞凋亡。结论:和厚朴酚能够抑制人皮肤鳞癌细胞A431的增殖并诱导凋亡,其机制可能与p53信号通路有关。     

奥沙利铂联合山柰酚动脉介入治疗抑制肺癌移植瘤大鼠肿瘤生长

目的:考察奥沙利铂（oxaliplatin）联合山柰酚（kaempferol）动脉介入治疗对裸大鼠肺癌移植瘤的生长抑制和诱导凋亡作用。方法:皮下接种A549肺癌细胞,将裸大鼠分为对照组、奥沙利铂静脉注射组、奥沙利铂联合山柰酚静脉注射组,和奥沙利铂联合山柰酚动脉介入治疗组。研究考察不同给药方式对实体瘤生长、对大鼠体重的影响。利用免疫荧光染色、Hoechst染色及免疫印迹法（western blot,WB）考察瘤组织细胞凋亡水平。结果:首先相比对照组,奥沙利铂静脉注射抑制实体瘤生长,相比奥沙利铂静脉注射组,奥沙利铂静脉注射联合山柰酚对实体瘤生长没有明显抑制作用,奥沙利铂动脉介入治疗联合山柰酚显著抑制实体瘤生长。其次山柰酚能逆转奥沙利铂对大鼠的体重抑制作用。最后,静脉注射治疗下,山柰酚能促进奥沙利铂对细胞凋亡的诱导作用,而动脉介入治疗更显著地促进药物联用引起的细胞凋亡作用。结论:奥沙利铂联合山柰酚动脉介入治疗可以显著抑制裸大鼠肺癌移植瘤生长并促进细胞凋亡。     

多烯紫杉醇抑制SMMC-7721肝癌细胞的研究

目的探索多烯紫杉醇对在体和离体SMMC-7721肝癌的生长抑制作用及其机制.方法(1)将SMMC-7721肝癌细胞种植于培养皿,贴壁后给予不同浓度的多烯紫杉醇作用24小时,10天后观察多烯紫杉醇对集落形成率的抑制作用;(2)多烯紫杉醇作用于SMMC-7721肝癌细胞24小时后,利用电子显微镜观察细胞凋亡的形态学特征,用流式细胞仪测定细胞周期的变化;(3)制备SMMC-7721肝癌荷瘤鼠模型,观察多烯紫杉醇诱导对在体SMMC-7721肝癌生长曲线和相对生长速率的影响.结果(1)多烯紫杉醇对离体和在体SMMC-7721肝癌细胞生长具有明显抑制作用,并且存在剂量依赖性;(2)多烯紫杉醇可以通过将肝癌细胞阻滞于G2-M期来发挥抗癌作用.结论多烯紫杉醇通过将肝癌细胞阻滞于G2-M期并且诱导肝癌细胞凋亡来发挥抗癌作用,是很有潜力的抗肝癌药物.     

胃癌干细胞的研究进展

随着恶性肿瘤基础研究的不断深入,肿瘤干细胞的存在被越来越多的基础和临床研究所证实。目前,包括血液系统肿瘤和实体瘤在内的多种肿瘤干细胞已被分离纯化和鉴定。胃癌作为目前在中国发病率和致死率最高的肿瘤之一,其具有肿瘤干细胞特性的胃癌细胞亚群已被分选出来,但多数研究对胃癌干细胞的特异性表面标志物尚不能达成共识,导致胃癌干细胞表面标志物未能明确。至今已有多项研究先后报道了不同表面标志物的胃癌干样细胞,它们中的大部分都可分化为其他具有不同表型的胃癌细胞,并可以在体外克隆成球及在免疫缺陷小鼠体内成瘤,符合肿瘤干细胞自我更新、多向分化、高效致瘤等特征。本文就近年胃癌干细胞及其分离鉴定方面的研究进展进行综述。     

分泌肿瘤坏死因子的基因工程细胞对HepG2细胞的抑制作用

目的自行建立分泌人肿瘤坏死因子α的基因工程细胞,将其与肝癌细胞共培养,观察体外培养中分泌肿瘤坏死因子hTNF/293基因细胞表达的情况及对人肝癌细胞的抑制作用。方法(1)建立可稳定分泌人肿瘤坏死因子α/293细胞;采用RT-PCR、Western blot、ELISA和流式细胞仪等技术检测人肿瘤坏死因子表达和分泌;(2)观察体外培养中分泌肿瘤坏死因子hTNF/293基因细胞对人肝癌细胞的抑制作用,于不同的时间点,用MTT法检测490 nm下的吸光度值。结果RT-PCR、Western blot和ELISA等技术检测表明hTNFα/293 细胞组和TNFα阳性组对共培养的HepG2细胞的增殖具有明显的抑制作用,且具有良好的量效关系。结论提示TNF-α/293基因细胞可有效分泌hTNFα蛋白,并能分泌到细胞外;体外培养的人肿瘤坏死因子基因的工程细胞,所分泌肿瘤坏死因子α对人肝癌细胞增殖有明显抑制效应,且呈现出良好的数量依赖关系。     

三种不同来源的围产期间充质干细胞条件培养基的抗癌能力比较

目的:探究羊水、脐带和胎盘三种不同来源间充质干细胞中,抑癌效果最好的间充质条件培养基。方法:应用羊水、脐带和胎盘三种不同来源间充质干细胞的不同浓度的条件培养基分别培养HELA、SKOV-3、MCF-7三种癌细胞,CCK-8法检测培养72 h后不同癌细胞的细胞活性;应用羊水、脐带和胎盘三种不同来源间充质干细胞条件培养基培养HELA细胞24、48、72、96 h后,利用CCK-8法检测癌细胞的细胞活性;采用Annexin V-FITC/PI通过流式细胞术检测条件培养基培养HELA细胞72 h后的癌细胞凋亡情况;qPCR鉴定条件培养基培养HELA细胞72 h后的癌症相关基因LOXL2、LIF、CatB、FOXQ1的表达,同时对不同间充质干细胞条件培养基培养后迁移的HELA细胞数量进行计算。结果:三种不同浓度的条件培养基均对癌细胞有抑制作用,其中浓度为100%条件培养基对癌细胞的抑制作用最好;三种不同来源间充质干细胞条件培养基均对癌细胞有抑制作用,且羊水间充质干细胞条件培养基培养HELA细胞72 h对癌细胞的抑制作用最强;流式细胞术与qPCR结果表明间充质干细胞条件培养基抑制HELA细胞生长的作用机制是通过促进其凋亡进行的;羊水间充质干细胞条件培养基培养后HELA细胞迁移数量最少。结论:羊水间充质干细胞是最适合用于抑制癌细胞生长的细胞,可以促进癌细胞凋亡,浓度为100%条件培养基培养癌细胞72 h对癌细胞抑制效果最好。     

Label retaining cells in cancer – The dormant root of evil?

The phenomenon of cellular dormancy has been observed in normal adult stem cells in many different tissues such as the skin, the intestine and the hematopoietic system. These dormant cells have been proposed to be important for life-long self-renewal and for the generation of the different cellular lineages. As tumor cells can share properties with normal stem cells, dormant cells might also exist within a tumor. The term tumor dormancy has evolved from the clinical observation in cancer patients that relapse can occur years to decades after apparently successful treatment, suggesting that some cancer cells might resist chemotherapy and persist in a dormant state. Several studies investigating the role of cellular dormancy in normal stem cells and in cancer hint towards a complex network involving different pools of cells. These cells might interact with each other or even dynamically switch their phenotypes dependent upon so far unknown endogenous and microenvironmental stimuli. In this review, we will discuss the recent findings related to cellular dormancy in normal adult stem cells and in cancer. Furthermore, the clinical relevance of dormancy and its dynamic regulation in tumor cells will be highlighted.     

Are cancer stem cells radioresistant?

Based on findings that cancer cell clonogens exhibit stem cell features, it has been suggested that cancer stem-like cells are relatively radioresistant owing to different intrinsic and extrinsic factors, including quiescence, activated radiation response mechanisms (e.g., enhanced DNA repair, upregulated cell cycle control mechanisms and increased free-radical scavengers) and a surrounding microenvironment that enhances cell survival mechanisms (e.g., hypoxia and interaction with stromal elements). However, these radiosensitivity features are probably dynamic in nature and come into play at different times during the course of chemo/radiotherapy. Therefore, different molecularly targeted radiosensitization strategies may be needed at different stages of therapy. This article describes potential sensitization approaches based on the dynamics and changing properties of cancer stem-like cells during therapy.     

O-glycosylation regulates LNCaP prostate cancer cell susceptibility to apoptosis induced by galectin-1

Resistance to apoptosis is a critical feature of neoplastic cells. Galectin-1 is an endogenous carbohydrate-binding protein that induces death of leukemia and lymphoma cells, breast cancer cells, and the LNCaP prostate cancer cell line, but not other prostate cancer cell lines. To understand the mechanism of galectin-1 sensitivity of LNCaP cells compared with other prostate cancer cells, we characterized glycan ligands that are important for conferring galectin-1 sensitivity in these cells, and analyzed expression of glycosyltransferase genes in galectin-1-sensitive, prostate-specific antigen-positive (PSA(+)) LNCaP cells compared with a galectin-1-resistant PSA(-) LNCaP subclone. We identified one glycosyltransferase, core 2 N-acetylglucosaminyltransferase, which is down-regulated in galectin-1-resistant PSA(-) LNCaP cells compared with galectin-1-sensitive PSA(+) LNCaP cells. Intriguingly, this is the same glycosyltransferase required for galectin-1 susceptibility of T lymphoma cells, indicating that similar O-glycan ligands on different polypeptide backbones may be common death trigger receptors recognized by galectin-1 on different types of cancer cells. Blocking O-glycan elongation by expressing alpha2,3-sialyltransferase 1 rendered LNCaP cells resistant to galectin-1, showing that specific O-glycans are critical for galectin-1 susceptibility. Loss of galectin-1 susceptibility and synthesis of endogenous galectin-1 has been proposed to promote tumor evasion of immune attack; we found that galectin-1-expressing prostate cancer cells killed bound T cells, whereas LNCaP cells that do not express galectin-1 did not kill T cells. Resistance to galectin-1-induced apoptosis may directly contribute to the survival of prostate cancer cells as well as promote immune evasion by the tumor.     

Colorectal cancer stem cell: a potential therapeutic target

The discovery of cancer stem cells has improved our understanding of tumour occurrence and development. Colorectal cancer stem cells may be derived from mutations in normal intestinal epithelial stem cells. CD133⁺ and aldehyde dehydrogenase 1 (ALDH1)⁺ cells have strong tumorigenic capacities and may represent different subpopulations of colorectal cancer stem cells. Multiple signalling pathways, especially the Wnt pathway, are important in colorectal cancer occurrence and development, and maintaining the stemness of colorectal cancer stem cells. Identifying colorectal cancer stem cells and understanding the related signalling pathways are important for developing new targeted interventions for colorectal cancer.     

How does a normal human cell become a cancer cell?

The mechanism by which cells become cancerous has been studied in several different species and cell types. Here, we will focus on the mechanism by which a normal human cell becomes a cancer cell and specifically discuss genes that researchers have used to transform cells. Studying how those genes affect cellular immortalization and transformation will help researchers understand more about cancer biology, find new treatments for cancer and/or improve cell survival during gene therapy.     

Inhibition of HSP70: A challenging anti-cancer strategy

HSP70 is a chaperone that accumulates in the cells after many different stresses promoting cell survival in response to the adverse conditions. In contrast to normal cells, most cancer cells abundantly express HSP70 at the basal level to resist to various insults at different stages of tumorigenesis and during anti-cancer treatment. This cancer cells addiction for HSP70 is the rational for its targeting in cancer therapy. Much effort has been dedicated in the last years for the active search of HSP70 inhibitors. Additionally, the recent clinical trials on highly promising inhibitors of another stress protein, HSP90, showed compensatory increase in HSP70 levels and raised the question of necessity to combine HSP90 inhibitors with simultaneous inhibition of HSP70. Here we analyzed the recent advancement in creation of novel HSP70 inhibitors and different strategies for their use in anti-cancer therapy.