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1.
毛兰素对人肝癌Huh7细胞的抑制作用   总被引:2,自引:0,他引:2  
研究了从鼓槌石斛中分离得到的低分子量天然化合物毛兰素在体外对人肝癌Huh7细胞的增殖抑制作用,并探讨其诱导细胞凋亡的分子机制.实验结果显示:毛兰素能显著抑制肝癌Huh7细胞的增殖,且随着药物浓度与时间增加其抑制率呈明显的剂量时间效应,其48 h半数抑制浓度IC50为37.4 nmol/L;毛兰素能诱导人肝癌Huh7细胞凋亡并使其细胞周期阻滞于G2-M期;分子机制研究显示毛兰素可抑制Akt激酶活性、下调Mcl-1蛋白表达以及激活PARP活性从而导致其对Huh7癌细胞的增殖抑制作用.以上结果初步表明毛兰素对肝癌防治具有潜在药用价值.图5参17  相似文献   

2.
目的:研究不同浓度生长抑素类似物奥曲肽对人结肠癌SW480细胞生长增殖的抑制作用.方法:体外培养人结肠癌SW480细胞;MTT比色法测定不同浓度奥曲肽抑制SW480细胞增殖作用,以效价强度最高者为最佳抑制浓度;然后,平皿集落形成法测定奥曲肽抑制体外培养SW480细胞的锚定依赖性生长作用.结果:不同浓度奥曲肽对SW480细胞增殖活性具有不同程度的抑制作用,在10-10 M-10-8M(mol/L)浓度范围内呈剂量依赖性,其中10-8M为最佳抑制浓度;奥曲肽对SW480细胞锚定依赖性生长具有明显的抑制作用,并呈浓度依赖性.结论:奥曲肽能抑制体外培养人结肠癌SW480细胞生长增殖,并在一定范围内呈浓度与时间依赖性.  相似文献   

3.
卡瓦胡椒素B是药用植物卡瓦胡椒根中的一种天然查耳酮类化合物,研究了其对人非小细胞肺癌A549细胞的增殖抑制作用及其诱导细胞凋亡的分子机制.实验结果显示,卡瓦胡椒素B能显著抑制非小细胞肺癌A549细胞的增殖,且随着药物浓度的增加、处理时间的延长其抑制作用呈明显的剂量时间效应;同时,卡瓦胡椒素B能显著诱导A549细胞凋亡、细胞周期阻滞于G2-M期;分子机制研究表明,卡瓦胡椒素B能通过活化JNK激酶活性、下调凋亡抑制蛋白survivin的表达以及激活PARP活性从而导致其对A549细胞的增殖抑制作用.结果表明卡瓦胡椒素B对人非小细胞肺癌的预防与治疗可能具有潜在价值.  相似文献   

4.
染料木黄酮诱导人结肠癌SW480细胞凋亡及机制   总被引:1,自引:0,他引:1  
目的探讨染料木黄酮(GEN)诱导人结肠癌SW480细胞凋亡的生物学效应及抗肿瘤机制.方法通过MTT法检测GEN对该细胞系生长的影响;应用PI染色流式细胞术(FCM)分析GEN处理前后的细胞周期分布的变化;SP免疫组化法检测细胞内bcl-2、Bax蛋白的表达.结果GEN能抑制SW480细胞增殖,呈浓度依赖性.流式细胞仪示不同浓度GEN作用于SW480细胞,出现G2/M阻滞;SP免疫组化结果表明GEN处理细胞72 h后,Bax蛋白表达升高,bcl-2蛋白表达下降.结论GEN有诱导人结肠癌SW480细胞凋亡的作用,其机制与bcl-2/Bax比值下降有关.图2,参12.  相似文献   

5.
蛋白质精氨酸甲基转移酶1(PRMT1)是近年来新发现的一种表观遗传修饰酶,在膀胱癌等多种癌组织中过度表达,因此针对该靶点的新型表观抗肿瘤药物研究尤为重要.通过基于PRMT1药效团虚拟筛选模型筛查抑制PRMT1活性的小分子化合物,体外研究了靶向PRMT1的小分子化合物DB75对膀胱癌细胞的抗瘤活性及诱导细胞凋亡的分子机制.实验结果显示:通过筛选体系获得了能显著抑制PRMT1活性的小分子化合物DB75;MTT实验表明,DB75能够显著(P<0.05)地抑制膀胱癌T24细胞的增殖,且随着药物浓度的增加,抑制率呈明显的剂量效应,48 h半数抑制浓度IC50为2.2μmol/L;DAPI染色显示DB75能显著(P<0.05)诱导膀胱癌T24细胞凋亡;分子机制研究显示,DB75通过激活Caspase-3和PARP活性从而诱导T24细胞凋亡.以上结果初步表明DB75可作为一种新型的膀胱癌表观先导化合物.  相似文献   

6.
通过溶剂萃取与重结晶等方法从银莲花属植物多被银莲花Anemone raddeana Regel根茎中提取三萜皂苷银莲花素A,研究银莲花素A对非小细胞肺癌H460癌细胞的增殖、凋亡与细胞周期的影响及分子机制.结果表明:银莲花素A能显著地抑制H460癌细胞的增殖,且这种抑制效应呈明显的时间量效关系;能诱导H460癌细胞凋亡,并诱导其细胞周期阻滞于G2-M期;能抑制Akt激酶活性、下调Bcl-2蛋白表达以及激活PARP活性,从而导致其对H460癌细胞的增殖抑制作用.结果显示银莲花素A对非小细胞肺癌的预防与治疗可能具有潜在价值.  相似文献   

7.
观察没食子酸丙酯(Propyl gallate,PG)对人慢性髓系白血病K562细胞株的增殖抑制及诱导凋亡作用.采用倒置显微镜观察细胞形态及数目的变化,乳酸脱氢酶(Lactate dehydrogenase,LDH)释放检测细胞活性,流式细胞术PI染色法及DNA倍体分析检测细胞凋亡作用.结果表明,没食子酸丙酯能有效地抑制K562细胞增殖,药物处理24 h时细胞形态发生变化,细胞数目减少;细胞培养液中LDH活性分析显示,20~300μg/mL没食子酸丙酯处理24 h对细胞毒性作用不明显;但处理时间达48 h时,没食子酸丙酯对细胞毒性明显增加;亚二倍体峰(凋亡峰)的出现及DNA片段化分析表明,200μg/mL PG处理细胞24 h时,能引起K562细胞凋亡.结果表明,PG具有明显的体外抗肿瘤活性,其抗癌活性与其抑制细胞增殖、诱导细胞凋亡有关.图5参18  相似文献   

8.
镉诱导大鼠肾细胞凋亡及其机理的研究   总被引:3,自引:2,他引:1  
为探讨镉(Cd)致大鼠肾细胞(NRK cell)凋亡的死亡受体途径,分别将终浓度为0、10、20、40、60μmol·L-1的CdCl2添加到培养液中,对NRK细胞暴露6h.应用流式细胞仪检测NRK细胞凋亡率;分光光度计检测Caspase-8蛋白活性;半定量RT-PCR检测Caspase-8、Fas的mRNA表达.结果表明,随着CdCl2暴露浓度的升高,NRK细胞凋亡率升高,Caspase-8蛋白活性增强,Caspase-8、Fas的mRNA表达增强,并呈现剂量-效应关系.说明镉可以通过死亡受体这条通路来引起NRK细胞凋亡.  相似文献   

9.
以原代培养的大鼠睾丸支持细胞为研究对象,选取环境及生物体中均有检出的一种典型的羟基化PBDE——6-HO-BDE-137作为目标化合物,设置0、0.1、1、10μmol·L-14个浓度梯度,应用噻唑蓝(MTT)试验、荧光显微镜观察和AnnexinV-FITC/PI双染流式细胞术,通过检测大鼠睾丸支持细胞增殖活性、细胞形态和细胞凋亡坏死率的变化,探讨其对支持细胞的损伤情况.研究发现,6-HO-BDE-137显著影响支持细胞的增殖活力,暴露24h,10μmol·L-1浓度组细胞与对照组相比显著增殖(p<0.05),随暴露时间的延长(至48h),10μmol·L-1组转为增殖抑制;支持细胞形态也表现出不同程度的改变,10μmol·L-1浓度组变化最为明显,有大量的细胞变圆飘起;随6-HO-BDE-137暴露浓度的升高,支持细胞死亡率增加,凋亡是支持细胞死亡的主要方式.研究结果提示:6-HO-BDE-137具有生殖毒性.  相似文献   

10.
应用基因芯片技术研究发现,暴露于五氯酚的斑马鱼胚胎中有14个涉及细胞凋亡行为的基因表达发生了显著改变.利用生物信息学方法构建这些功能基因系统进化树,分析与环境毒物诱导的细胞凋亡行为密切相关的caspase-2基因和其他基因之间的同源关系.斑马鱼caspase-2基因由10个外显子和9个内含子组成,cDNA长1308bp,含一个开放阅读框(ORF),编码435个氨基酸.6种脊椎动物Caspase-2氨基酸序列的保守性及系统进化分析结果表明,在特定功能区结构域中氨基酸序列表现出较高的同源性,Caspase-2在进化上高度保守.利用RT-PCR技术,斑马鱼caspase-2基因cDNA被克隆并确认.研究结果表明斑马鱼caspase-2基因是一个研究细胞凋亡行为的模型分子,可为环境化合物的分子毒性评价及其机制研究提供一种分子标记。  相似文献   

11.
● State-of-the-art applications of machine learning (ML) in solid waste (SW) is presented. ● Changes of research field over time, space, and hot topics were analyzed. ● Detailed application seniors of ML on the life cycle of SW were summarized. ● Perspectives towards future development of ML in the field of SW were discussed. Due to the superiority of machine learning (ML) data processing, it is widely used in research of solid waste (SW). This study analyzed the research and developmental progress of the applications of ML in the life cycle of SW. Statistical analyses were undertaken on the literature published between 1985 and 2021 in the Science Citation Index Expanded and Social Sciences Citation Index to provide an overview of the progress. Based on the articles considered, a rapid upward trend from 1985 to 2021 was found and international cooperatives were found to have strengthened. The three topics of ML, namely, SW categories, ML algorithms, and specific applications, as applied to the life cycle of SW were discussed. ML has been applied during the entire SW process, thereby affecting its life cycle. ML was used to predict the generation and characteristics of SW, optimize its collection and transportation, and model the processing of its energy utilization. Finally, the current challenges of applying ML to SW and future perspectives were discussed. The goal is to achieve high economic and environmental benefits and carbon reduction during the life cycle of SW. ML plays an important role in the modernization and intellectualization of SW management. It is hoped that this work would be helpful to provide a constructive overview towards the state-of-the-art development of SW disposal.  相似文献   

12.
Epigenetic change is a key factor for esophageal cancer progression. This study shows that upon exposure of primary cultures of human esophageal epithelial cells obtained from people of the Kazakh nationality in China to N-methyl-N′-nitro-N-nitrosoguanidine at concentrations of 0.75, 1.50, and 3.00 mg/L, (1) cell proliferation was inhibited, the percentages of cells in the G0 and G1 phases declined, and those in the S and G2 + M phases increased at all concentrations, while apoptosis rates increased at medium and high concentrations; (2) the content of DNA-methyltransferases 3a and 3b and the activities of DNA-methyltransferase 1 and DNA-methyltransferase 3a increased at all concentrations while the content of DNA-methyltransferase 1 and the activity of DNA-methyltransferase 3b were increased only at the high concentration; (3) messenger RNA and protein levels of DNA-methyltransferases 1, 3a, and 3b were increased at all concentrations. Obviously, N-methyl-N′-nitro-N-nitrosoguanidine in the low mg/L range can inhibit the proliferation of normal Kazakh esophageal epithelial cells, can cause cell cycle arrest in the S and G2 + M phases, promote apoptosis, and increase the activities of DNA-methyltransferases 1, 3a, and 3b.  相似文献   

13.
The molecular mechanisms underlying proliferation and apoptosis induced by p-nonylphenol (NP) through regulation of mRNA and protein expression of c-myc, p53 mRNA and the protein was investigated using ovarian cancer PEO4 cells. PEO4 cells were grown in the Dulbecco's modified Eagle medium (DMEM), 3(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay was employed to investigate cell proliferation. RT-PCR and immunohistochemistry was performed to determine mRNA and protein expression of PEO4 c-myc and p53. Within the range of approximately 8–9×10?7 mol L?1, NP stimulated proliferation in PEO4 cells in a concentration-and time-dependent manner. RT-PCR and immunohistochemistry analyses revealed that treatment with 32 × 10?7 mol L?1 NP for 72 hr resulted in increased mRNA and protein expression of PEO4 c-myc and p53. Evidence indicates that NP exerted estrogenic actions and stimulated proliferation in estrogen responsive ovarian cancer PEO4 cells by up-regulation of c-myc mRNA and protein expression.  相似文献   

14.
The marine toxin, okadaic acid (OA) is produced by dinoflagellates of the genera Prorocentrum and Dinophysis and is the causative agent of the syndrome known as diarrheic shellfish poisoning. In addition, OA acts as both a tumor promoter, attributed to OA-induced inhibition of protein phosphatases as well as an inducer of apoptosis. To better understand the potentially divergent toxicological profile of OA, the concentration-dependent cytotoxicity and alterations in gene expression on the human liver tumor cell line HepG2 upon OA exposure were determined using RNA microarrays, DNA fragmentation, and cell proliferation assays as well as determinations of cell detachment and cell death in different concentrations of OA. mRNA expression was quantified for approximately 15,000 genes. Cell attachment and proliferation were both negatively correlated with OA concentration. Detached cells displayed necrotic DNA signatures but apoptosis also was broadly observed. Data suggest that OA has a concentration dependent effect on cell cycle, which might explain the divergent effects that at low concentration OA stimulates genes involved in the cell cycle and at high concentrations it stimulates apoptosis.  相似文献   

15.
为观察牛磺熊脱氧胆酸(Tauroursodeoxycholic acid,TUDCA)对棕榈酸(Palmitate)诱导的INS-1细胞凋亡的影响,分别用不同浓度棕榈酸(0.25mmol·L-1、0.5mmol·L-1、1.0mmol·L-1),棕榈酸(0.5mmol·L-1)+不同浓度TUDCA(25μmol·L-1、50μmol·L-1、100μmol·L-1)培养INS-1细胞12h,用MTT法检测细胞毒性作用,流式细胞术检测细胞凋亡,RT-PCR技术检测凋亡相关基因Bax/Bcl-2的表达.结果表明,与空白对照组比较,棕榈酸组(浓度≥0.5mmol·L-1)INS-1细胞凋亡率显著上升(p<0.05);加TUDCA培养组,当浓度≥50μmol·L-1时,与棕榈酸组相比,INS-1细胞凋亡率显著下降(p<0.05),呈剂量-效应关系.此外,棕榈酸组(浓度≥0.5mmol·L-1)INS-1细胞凋亡相关基因Bax表达显著上升(p<0.05),Bcl-2则明显下降;加TUDCA后,Bax基因表达显著下降(p<0.05),而Bcl-2则明显上升(p<0.05),并呈剂量-效应关系.以上结果表明,TUDCA能够减少游离脂肪酸引起的INS-1细胞凋亡,对INS-1细胞发挥保护作用.而凋亡促进基因Bax的表达下调,凋亡抑制基因Bcl-2的表达上调可能是其作用机制之一.  相似文献   

16.
Phenoxyherbicides induce peroxisome proliferation, as do other structurally related or unrelated chemicals which were found to be nongenotoxic carcinogens in rodents. The widespread use of 2,4-dichlorophenoxyacetic acid (2,4-D) raised concerns over the potential to produce cancer, yet results from epidemiological and experimental studies do not provide definitive evidence that 2,4-D is carcinogenic. The objective of the present study was to verify whether 2,4-D might interfere with cell growth similar to other peroxisome proliferators using cultured avian hepatocytes. Primary hepatocyte cultures from 18-day-old chick embryos were exposed to 2,4-D for up to 72 h followed by an assessment of replicative DNA synthesis and apoptosis. Further, peroxisome proliferation was evaluated. Results showed that 2,4-D stimulated DNA synthesis and suppressed spontaneous apoptosis, while the effects on peroxisome proliferation were less evident.  相似文献   

17.
Vero细胞对2,4,6-三氯苯酚的毒性响应特征和敏感性分析   总被引:2,自引:1,他引:1  
以2,4,6-三氯苯酚(2,4,6-trichlorophenol,TCP)为例,采用MTT比色实验和ANNEXIN V-FITC/PI双染色-流式细胞技术研究了Vero细胞对有机化学污染物的毒性响应特征和敏感性,以期发现一种灵敏、可靠的表征微量化学物质综合毒性的方法.研究结果表明:1)TCP浓度对Vero细胞的毒性响应特征有决定作用.低浓度TCP(≤0.5mg·L-1)即可使部分细胞从原有的刚性不规则三角形结构变为圆形或椭圆形,但细胞的生长未受明显抑制.TCP浓度在1~5mg·L-1时,细胞生长开始受到抑制,表现为细胞增殖受到抑制及部分细胞凋亡或死亡,但增殖抑制率和TCP浓度之间的关系不明显.当TCP浓度大于5mg·L-1时,细胞增殖明显受到抑制,且随TCP浓度的增加,细胞增殖抑制率逐渐升高.2)TCP作用时间对Vero细胞的毒性响应特征有显著影响.ANNEXIN V-FITC/PI双染色-流式细胞仪检测结果表明,TCP作用24h内Vero细胞毒性表现为以细胞膜的完整性受到损伤为主,凋亡或坏死细胞比例较小;而48h后,凋亡细胞的比例明显增加.细胞复壮实验结果进一步证实24h内形态发生变化的细胞并未完全坏死或凋亡.以上结果表明细胞形态变化和细胞膜损伤均为细胞毒性的早期表现特征,两者之间可能存在某种相关性,以此表征化学污染物的生物毒性具有较高的灵敏度,值得进一步研究.  相似文献   

18.
Arsenic is a significant environmental concern worldwide, primarily due to geo physiochemical contamination of drinking water, and a major public health hazard in both developing and developed countries. The present study was aimed to investigate ameliorative effects of curcumin (Cur) against sodium arsenite (SA)-induced toxicity in cultured murine Sertoli cells. The cells were treated with SA (5 μM) and Cur (5 μg/ml and 10 μg/ml) alone or in combination for 12 hr. The SA treatment decreased cell viability, produced oxidative stress, and induced apoptosis as reflected by reactive oxygen species (ROS) generation, loss of mitochondrial transmembrane potential, DNA fragmentation, and apoptotic cells. Moreover, the SA-induced cell cycle arrest in the cells is characterized by a rise in the number of cells in the sub G1 phase of the cell cycle. The Cur was found to be effective in reversing all these arsenic (As)-induced cellular events. Data suggest that Cur modulates As-mediated oxidative stress, apoptosis, DNA fragmentation, and cell cycle arrest through suppression of excessive ROS generation. Evidence indicates that Cur may emerge as a useful protective agent against As-induced Sertoli cells toxicity by inhibiting As-induced damage in testes.  相似文献   

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