Glucose toxicity for human endothelial cells in culture. Delayed replication, disturbed cell cycle, and accelerated death

Functional and anatomical abnormalities of endothelium may represent a pathway to the increased vascular permeability and accelerated atherosclerosis characteristic of diabetes. To identify whether and how hyperglycemia may compromise the endothelial barrier, we have employed an in vitro system of human endothelial cells obtained from umbilical veins and cultured in elevated glucose concentrations (20 mM). Under these conditions, the achievement of saturation density was substantially delayed, with cell counts throughout most of the growth curve being 70-80% of control (P less than 0.002). More profound suppression of cell number was present in cultures exposed to 40 mM glucose. Similar, albeit slightly lesser, effects were observed in cultures exposed to 20 mM mannitol, mimicking the hypertonicity of the high glucose media. The effect of elevated glucose and mannitol was primarily mediated by a decrease in overall rate of replication of the endothelium as documented by the lower mitotic index (P less than 0.025). Analysis of the distribution of cells along phases of the cell cycle uncovered in the high glucose cultures a decreased proportion of cells in G0-G1 (70.5 +/- 5% versus 73.2 +/- 4% in controls, P less than 0.05) and an increased proportion of cells in S phase (16.5 +/- 2.7% versus 13.5 +/- 2.2% in controls, P less than 0.01), suggesting that the replicative delay is likely to occur between the phase of DNA synthesis and mitosis. Increased cellular death was specifically observed in the cultures exposed to elevated glucose concentrations (P less than 0.05), but it could account for only a minor portion of the deficit in cell number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modification of tissue-factor mRNA and protein response to thrombin and interleukin 1 by high glucose in cultured human endothelial cells

Because diabetic vascular disease is accompanied by a state of hypercoagulability, manifested by increased thrombin activity and foci of intravascular coagulation, we investigated whether a specific procoagulant property of the endothelium--production and surface expression of tissue factor--is modified by elevated glucose concentrations. In unperturbed human vascular endothelial cells, tissue factor mRNA and expression of the functional protein were undetectable and were not induced by 10-12 days of exposure to 30 mM glucose. In thrombin-stimulated cultures, tissue-factor expression was related inversely to cellular density, with confluent cultures producing (per 10(5) cells) half the amount of tissue factor measured in sparse cultures. Cells exposed to high glucose and studied when cell number and thymidine incorporation were identical to control cells manifested increased tissue-factor mRNA level and functional protein production in response to thrombin (P = .002). This effect was not attributable to hypertonicity and was not observed after short exposure to high glucose. In contrast, the tissue-factor response to interleukin 1, a modulator of endothelial function in the context of host defense, was decreased in cells cultured in high glucose (P = .04). These findings indicate that exposure to high glucose can alter tissue-factor gene expression in perturbed vascular endothelium. The reciprocal effects of high glucose on the tissue-factor response to thrombin and interleukin 1 points to different pathways of tissue-factor stimulation by the two agents and suggests functional consequences pertinent to the increased thrombin activity and compromised host-defense mechanisms observed in diabetes.     

EGCG对高糖环境下小鼠足细胞增殖和P21^Cip1、P27^Kip1表达的影响

目的：研究作为绿茶主要活性成分的EGCG对高糖环境下足细胞增殖和周期素激酶抑制剂P21^Cip1和P27^Kip1表达的影响,从而探讨其作用机制。方法：以高糖（25mmol/L）培养的小鼠足细胞为研究对象,维生素E为对照,以不同浓度EGCG（0.2,10,100μmol/L）培养24h、48h、72h,首先以相差显微镜观察足细胞形态改变;其次,以BrduELISA法检测细胞增殖;流式细胞仪分析足细胞G1/G0、S期、G2/M期百分比;RT-PCR检测细胞周期依赖型蛋白激酶抑制剂P21^Cip1mRNA和P27^Kip1mRNA表达。结果：（1）相差显微镜下观察,高糖刺激后24h,部分足细胞脱落,呈不规则形态。（2）BrduELISA法以正常糖为对照,高糖刺激24h后,足细胞增殖无统计学差异,48h和72h后足细胞增殖减少,有统计学差异（P〈0.05）;以高糖组为对照,高糖刺激24h,维生素E组和维生素E＋EGCG协同作用组促进足细胞增殖有统计学差异（P〈0.05）,EGCG（0.2,10,100μmol/L）作用组无统计学意义;48h实验结果和24h相同;72hEGCG（100μmol/L）维生素E组和维生素E＋EGCG协同作用组促进足细胞增殖作用有统计学差异（P〈0.01）。（3）不同浓度EGCG对高糖刺激后足细胞周期G1/G0期、S期、G2/M期百分比无统计学差异（P〉0.05）。（4）RT-PCR高糖刺激后24h,足细胞P21^Cip1mRNA表达有上升,但无统计学意义（P〉0.05）;随EGCG浓度增加,以维生素E为对照,P21^Cip1mRNA表达无统计学差异（P〉0.05）。正常糖组为对照,高糖刺激后24h足细胞P27^Kip1mRNA表达上调,有统计学差异（P〈0.01）,随EGCG浓度增加,P27^Kip1mRNA表达无统计学差异（P〉0.05）。结论：EGCG（100μmol/L）作用72h促进高糖环境下足细胞增殖,对细胞周期作用不明显,高糖刺激后24h足细胞P27^Kip1mRNA表达上调,EGCG对足细胞细胞周期依赖型蛋白激酶抑制P21^Cip1mRNA和P27^Kip1表达无明显影响,提示EGCG促高糖环境下足细胞增殖作用可能还存在其他机制。     

咖啡酸苯乙酯对大肠癌SW480细胞生长和周期的影响

目的　探讨咖啡酸苯乙酯 (CAPE)对体外培养的大肠癌细胞SW 4 80增殖和细胞周期的影响。方法　不同浓度CAPE处理体外培养的大肠癌SW 4 80细胞后 ,采用MTT法检测细胞的增殖活性 ;流式细胞仪检测细胞周期分布。结果　CAPE处理SW 4 80细胞后 ,SW 4 80细胞的生长抑制率明显升高 ,抑制作用表现为剂量依赖性和时间依赖性。流式细胞仪细胞周期分析表明CAPE作用 2 4h后 ,细胞G0 /G1期比例上升 ,S期比例下降。同时发现CAPE作用后 ,细胞出现胞浆混浊 ,胞体缩小、变圆、皱缩 ,核固缩粹裂等凋亡形态学特征。结论　CAPE对大肠癌SW 4 80细胞株具有明显的生长抑制作用 ,其作用机制与阻滞细胞周期G1期和诱导细胞凋亡有关。     

巨噬细胞移动抑制因子对人结肠癌细胞增殖和血管形成的影响

目的:探讨巨噬细胞移动抑制因子（MIF）对人结肠癌细胞增殖和血管形成的影响。方法:检测不同浓度的抗MIF抗体（Anti-MIF）对人HCT-116结肠癌细胞株增殖及对血管内皮细胞生长因子（VEGF）的表达影响。结果:100，200，400，800 μg/L Anti-MIF处理HCT-116细胞48，72 h后，细胞增殖明显受到抑制，且呈时间-剂量依赖性。100，200，400，800 μg/L Anti-MIF处理HCT-116细胞72 h后，流式细胞仪细胞周期分析表明G0/G1期细胞百分率上升，S期和G2/M期细胞百分率下降;与阴性对照组相比，Anti-MIF作用72 h后VEGF蛋白表达明显减弱，并呈剂量依赖性（P＜0.05）。结论:MIF参与调节细胞的生长周期，并可能通过VEGF影响肿瘤血管形成，而在结肠癌的发病中发挥重要作用。     

Activation of cyclin D1-Cdk4 and Cdk4-directed phosphorylation of RB protein in diabetic mesangial hypertrophy

To determine the role of cell-cycle proteins in regulating pathological renal hypertrophy, diabetes was induced in mice expressing a human retinoblastoma (RB) transgene and in wild-type littermates. Whole-kidney and glomerular hypertrophy caused by hyperglycemia was associated with specific G1 phase cell-cycle events: early and sustained increase in expression of cyclin D1 and activation of cyclin D1-cdk4 complexes, but no change in expression of cyclin E or cdk2 activity. Overexpression of RB alone likewise caused hypertrophy and increased only cyclin D1-cdk4 activity; these effects were not further augmented by high glucose. Identical observations were made when isolated mesangial cells conditionally overexpressing RB from a tetracycline-repressible system hypertrophied in response to high glucose. A mitogenic signal in the same cell-culture system, in contrast, transiently and sequentially activated both cyclin D1-cdk4 and cyclin E-cdk2. In vivo and in cultured mesangial cells, high glucose resulted in persistent partial phosphorylation of RB, an event catalyzed specifically by cyclin D1-cdk4. These data indicate that mesangial hypertrophy caused by hyperglycemia in diabetes results in sustained cyclin D1-cdk4-dependent phosphorylation of RB and maintenance of mesangial cells in the early-to-middle G1 phase of the cell cycle.     

Differential regulation of connexin 26 and 43 in murine neocortical precursors

Proliferating cells of the developing murine neocortex couple together into clusters during neurogenesis. Previously, we have shown that these clusters contain neural precursors in all phases of the cell cycle except M phase, and that they extend a nestin-expressing process from the cluster to the pial surface. In addition, coupling within neocortical cell clusters is a dynamic process related to the cell cycle, with maximal coupling in S/G2 phase, uncoupling in M phase and then recoupling during G1 and S phases of the cell cycle. In the present study, we use immunohistochemistry to demonstrate that cycling neocortical cells as well as radial glial cells express the gap junction proteins connexin 26 and connexin 43. Furthermore, we demonstrate that biocytin labeled clusters extend processes to the pial surface that express the glial cell antigen RC2. Lastly, by combining bromodeoxyuridine and connexin immunohistochemistry on acutely dissociated neocortical cells, we show that the percentage of cycling cells immunoreactive to connexin 26 and connexin 43 changes through the cell cycle. These results indicate that radial glial cells as well as neural precursors couple into clusters, and suggest that through differential regulation of connexins, neocortical precursors may compartmentalize as they progress through the cell cycle.     

Dual roles for NF-kappaB activation in osteoblastic cells by serum deprivation: osteoblastic apoptosis and cell-cycle arrest

To clarify the mechanisms of osteoblastic cell death, we examined whether serum deprivation would cause activation of the apoptotic signal cascade and arrest of the cell cycle in mouse osteoblastic MC3T3-E1 cells. Serum withdrawal from osteoblastic cell cultures resulted in growth arrest and cell-cycle arrest at G0/G1, which actions were accompanied by transient and potent activation of NF-kappaB, caspase-8, caspase-2, caspase-3, and caspase-9 in this order. Apoptosis, but not necrosis, in serum-deprived cells could be detected by FACS using Annexin-V/propidium iodine double staining. Serum deprivation also resulted in transient activation of the 20S proteasome, which is an important component for regulation of the cell cycle by the ubiquitin-proteasome system. The 20S proteasome inhibitor (PSI) but not NF-kappaB inhibitor SN50 suppressed the activation of proteasomes in serum-deprived cells. Although caspase inhibitors could not prevent the G0/G1 arrest in the serum-deprived cells, SN50 and the 20S proteasome inhibitor could block it. Since SN50, 20S proteasome inhibitor and caspase inhibitor could rescue cells from serum deprivation-induced apoptosis, the pathway for NF-kappaB/caspase activation is independent of the NF-kappaB/cell-cycle pathway, and the events downstream of the NF-kappaB/caspase-9 cascade lead to apoptosis. Taken together, our present results identify a novel role for NF-kappaB in cell-cycle and apoptosis regulation and underscore the significance of each independent signal cascade in serum-deprived osteoblastic cells.     

热打击对培养人脐静脉内皮细胞增殖能力的影响

目的：研究梯度热打击对体外培养人脐静脉内皮细胞（HUVEC）增殖的影响.方法：设置培养HUVEC细胞的温度梯度（39、41、43 ℃）进行热打击1 h,相差显微镜观察细胞形态学改变,CCK-8比较细胞增殖率,流式细胞术研究细胞周期改变.结果：与正常对照组比较,1 h热打击结束时,各热打击组均出现部分细胞形态变圆,伪足变短,细胞间隙增大,以43 ℃组为明显.随热打击程度加深,未伸展细胞占培养细胞百分比增加（P〈0.05）.细胞增殖实验显示,与正常对照组比较,热打击后24 h,41 ℃和43 ℃组增殖率显著下降（P〈0.01）,48 h时仅43 ℃组增殖率显著下降（P〈0.05）,至72 h,各热打击组与正常对照组无显著差异.流式细胞术检查显示,1 h热打击结束即刻,与正常对照组比较,各热打击组细胞呈现显著的G0/G1期阻滞,以43 ℃组最显著（P〈0.05）;至48 h时各热打击组细胞周期基本恢复正常.结论：热打击对HUVEC具有细胞毒效应,可抑制HUVEC的增殖,造成细胞周期G0/G1期阻滞.     

超声消融术对癌细胞超微结构和细胞周期的影响

目的探讨超声消融术对癌细胞超微结构和细胞周期的影响. 方法体外超声消融(42 kHz,0.22 W)Walker-256细胞,扫描电镜、透射电镜和流式细胞仪分别观察细胞变化. 结果超声消融Walker-256细胞后,电镜观察发现:细胞膜破裂、细胞器紊乱不清、核染色质碎裂,提示细胞已受到严重的损伤.流式细胞仪检查发现,随着超声剂量的增大,细胞S期下降,G2 M期增加,说明细胞合成抑制,放射敏感性增加. 结论在细胞水平验证了超声消融术对癌细胞具有杀伤效应.     

雌激素对大鼠前列腺平滑肌细胞增殖的影响

目的 观察17β-雌二醇(E2)对大鼠前列腺平滑肌细胞(PSMC)增殖的影响.方法 取体重(253±28)g的雄性SD大鼠30只,无菌切取前列腺,应用酶消化法行原代细胞培养.取3～4代传代细胞,分别加入不同浓度E2(0.1～100)nmol/L处理72 h,应用流式细胞仪检测细胞周期、细胞凋亡及其相关蛋白Cyclin D1,应用western blot法检测bcl-2和bax表达.结果 E2(1、10 nmol/L)促进PSMC从G1期向S期过渡,其S期细胞比率分别为(18.50±4.98)%、(21.16±4.83)%,显著高于对照组(12.39±2.64)%(P＜0.05),并伴随Cyclin D1蛋白表达显著增高.而高浓度E2(100 nmol/L)则抑制细胞增殖,其S期细胞比率为(7.98±1.92)%,显著低于对照组(P＜0.05),并伴随bax表达显著增加和细胞凋亡率显著升高.结论 低浓度E2能够上调CyclinD1表达加速G1期向S过渡从而促进大鼠PSMC增殖,高浓度E2则通过增加bax表达促进细胞凋亡.     

High glucose accelerates the life cycle of the in vivo exposed mesothelium

BACKGROUND: Mouse mesothelium exposed in vivo for 30 days to high glucose solutions develop morphological changes that characterize a population of cells near the end of their life span. METHODS: The present study was designed to explore, in mesothelial cell imprints, whether these changes could derive from an early acceleration of the cell population life cycle in mice exposed for periods of up to 30 days to a 4.25% glucose fluid (236 mmol/L/L) prepared in Hank's balanced salt solution (HBSS). Three critical points of the cell's life cycle were evaluated: the G1 checkpoint [proliferating cell nuclear antigen (PCNA) expression], DNA synthesis ((3)H-thymidine incorporation), and the prevalence of mitosis. RESULTS: Cell populations exposed to a high glucose concentration showed an initial acceleration of their life cycle, as sustained by a peak of mitosis at two hours, an early increase of DNA incorporation sustained during the first 24 hours, as well as a top level of PCNA expression after three to four hours. These significantly higher values, compared with the control animals treated with HBSS, collapsed after 24 hours and were nil after 30 days of exposure. CONCLUSIONS: Exposure to a high glucose concentration induced an early and short-lived acceleration of the mesothelial cell cycle, and with a longer exposure this was followed by a depletion of the growth capabilities of the exposed monolayer.     

3-甲基腺嘌呤对大鼠内皮祖细胞增殖、凋亡及细胞周期的影响

目的 观察3-甲基腺嘌呤(3-methlyadenine,3-MA)对大鼠骨髓源性内皮祖细胞(endothelial progenitor cells,EPCs)增殖、凋亡及细胞周期的影响.方法 密度梯度法取大鼠骨髓EPCs,体外诱导分化并鉴定.实验分对照及不同浓度(1.25、2.5、5、10 mmol/L)3-MA组.四氮唑蓝(methyl thiazolyl tetrazolium,MTT)法测细胞增殖,流式细胞仪测凋亡率及细胞周期.结果 (1)5 mmol/L组促EPCs增殖;10 mmol/L组抑制EPCs增殖,差异有统计学意义(P＜0.05).其余两组对EPCs增殖无明显影响,差异无统计学意义(P＞0.05).(2)10 mmol/L组促EPCs凋亡,差异有统计学意义(P＜0.05).其余各组对EPCs凋亡率无明显影响,与对照组比较差异无统计学意义(P＞0.05).(3)5、10 mmol/L组影响细胞周期,5 mmoL/L组G0/G1期细胞减少、S和G2/M期增加;10 mmol/L组发生S期阻滞,G2/M细胞减少;差异有统计学意义(P＜0.05).结论 3-MA对EPCs增殖及凋亡的影响与其浓度有关,当浓度为10 mmol/L时抑制增殖并促进凋亡.

Abstract：

Objective To investigate the effect of proliferation,apoptosis and cell cycle of 3-MA on rat endothelial progenitor cells. Methods Bone marrow-derived mononuclear cells were isolated from rat bone marrow by ficoll. There were five groups. The control group and four 3-MA concentration groups: 1. 25 mmol/L,2. 5 mmol/L,5 mmol/L, 10 mmol/L. MTT was used to measure the proliferation of endothelial progenitor cells. Flow cytometry ( FCM) was used to detect cell apoptosis and cell cycle. Results (1)5 mmol/L 3-MA promotes proliferation of endothelial progenitor cells, while 10 mmol/L 3-MA inhibits the proliferation of endothelial progenitor cells (P ＜ 0. 05). (2) 10 mmol/L 3-MA promotes apoptosis of endothelial progenitor cells, compared with the control, the difference was significant ( P ＜ 0. 05 ). (3) 3-MA at the concentration of 5 mmol/L reduces cells at G0/G1 phase and increases S and G2/M phase cells; 10 mmol/L 3-MA induces endothelial progenitor cells blockade at S phase, G2/M phase cells decreased, compared with the control, the difference was significant (P ＜ 0. 05). Conclusions 5 mmol/L 3-MA promotes the proliferation of endothelial progenitor cells. 10 mmol/L 3-MA inhibits the proliferation and promotes apoptosis of endothelial progenitor cells.     

The anticancer effects of high energy shock waves on rat bladder cancer induced by BBN

The in vivo anticancer effects of high energy shock waves (HESW), on bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), were studied in the rat using the Siemens lithotriptor (Lithostar). There was no significant difference in the anticancer effects in delaying tumor growth, measured as the whole bladder weight including the weight of the cancer, between the groups with and without exposure to HESW. However, light microscopic examination revealed extensive submucosal bleeding and exfoliation of mucosa, and electron microscopic examination revealed degeneration of pleomorphic microvilli, swelling of mitochondria, and destruction of mitochondrial cristae in the cancer cells in bladders exposed to HESW. Flow cytometric determination of DNA content in the cancer cells exposed to HESW indicated a selective diminution of cells in the G2 and M phases and an increase of cells in the G0 and G1 phases of the cell cycle. While the mechanism of HESW-induced anticancer effect could not be determined on the basis of this study, these changes in the morphology and the cell cycle of cancer cells induced by HESW exposure suggest some kind of biological effects following exposure to HESW. It is expected that HESW be an effective method for the treatment of human cancer in combination with chemotherapy and radiation.     

X线照射对胆囊癌GBC-SD细胞增殖周期的影响

目的：探讨X线照射对胆囊癌细胞系GBC—SD的生长及对细胞增殖周期的影响。方法：分别给予体外培养的人胆囊癌细胞系GBC—SD以0,5,10,20Gy X线照射。通过MTT方法测定在不同剂量X线照射下的细胞生长变化。通过流式细胞仪检测胆囊癌细胞于照射后增殖周期时相的变化。结果：较大剂量的X线能抑制胆囊癌GBC-SD细胞系的生长,24h表现出明显的抑制作（P=0．002）;72h抑制作用更加显著（P〈0．001）：其作用呈现效应．剂量依赖性。流式细胞仪检测发现不同的剂量照射后,处于细胞周期不同阶段的细胞会发生不同的变化。24h：胆囊癌细胞的G0-G1、S期细胞比例减少．G2-M期细胞比例增加。72h：胆囊癌细胞的G0-G1细胞比例增加,S期、G2-M期细胞比例减少。实验同时发现小剂量的照射可刺激胆囊癌细胞的增殖,使S、G2-M期细胞增加;而提高照射剂量,使胆囊癌细胞生长停滞在G0～G1期．而S期、G2-M细胞百分比减少。结论：X线照射可通过改变细胞增殖周期分布比例抑制胆囊癌GBC-SD细胞的生长：增加照射剂量可提高胆囊癌的治疗疗效。     

热打击对培养肠黏膜上皮细胞IEC-6细胞活性和增殖的影响

目的：研究梯度热打击对体外培养肠黏膜上皮细胞活性和增殖的影响。方法：肠黏膜上皮细胞株IEC-6经培养后分为正常对照组（37℃、5％CO2培养箱培养）及39℃、41℃、43℃热打击组（分别在相应温度培养箱中培养）,相差显微镜观察各组细胞培养1h的形态学改变,CCK8法比较各组细胞培养0、1、3、5、7h的细胞活性和24h增殖率,流式细胞术研究细胞周期的改变。结果：与正常对照组比较,各热打击组各个时相细胞形态变圆,伪足变短,细胞间隙增大,活力下降（P〈0．01）。24h细胞增殖实验显示,与正常对照组比较,39℃组7h及41℃和43℃组各时相增殖率显著下降（P〈0．01）,呈时间及温度依赖关系。流式细胞术检查显示,热打击组细胞呈现细胞周期G0／G1和G2／M期阻滞。结论：热打击对IEC-6细胞具有细胞毒效应,可抑制IEC-6细胞的增殖,造成细胞周期G0／G1和G2／M期阻滞。     

Effect of controlled electromagnetic radiation on the growth of cells in tissue culture

Various mammalian and bacterial cell lines were exposed to microwave radiation at a wavelength of 12 cm, a frequency of 2.45 × 10⁹ cps, and a current at 120 mA under strictly controlled temperature conditions. Microwave radiation appeared to have a specific “nonthermal” inhibitory effect on the growth of mammalian cells. The various cell lines showed different sensitivities to exposure. L60T cells were susceptible to microwave exposure only during the M and G1 phases of the cell cycle. It was possible to markedly suppress the growth of asynchronous populations of L60T cells by exposing them to microwave energy at four successive 4-hr intervals, as culture progressively entered the M and G1 phases of the cell cycle.     

D-甲硫氨酸联合化疗对胃癌细胞株代谢周期的影响

目的:通过体外实验观察D-甲硫氨酸(D-Met)合并应用细胞周期特异性化疗药物对胃癌细胞株代谢周期的影响。方法:将人胃癌细胞株SGC-7901分别置于含L-Met、D-Met或以同型半胱氨酸替代Met(Met-Hcy+)的不同培养基中,或在上述诸培养基中分别加入5-氟脲嘧啶(5-FU)。培养48h后,应用流式细胞仪检测细胞周期和凋亡细胞的比例。结果:G0/G1期和G2/M期细胞的比例均示D-Met和Met-Hcy+组低于L-Met组,而S期细胞比例则示D-Met组最高,凋亡细胞比例也以D-Met组诸组为最高;与未加入化疗药物诸组相比,联合应用5-FU后,各组的G0/G1期细胞比例增高,S期和G2/M期细胞比例降低,凋亡细胞比例有所增高。结论:D-Met可干扰人胃癌细胞株的代谢周期,趋向阻滞肿瘤细胞于S期,有助于周期特异性化疗药物5-FU对此期肿瘤细胞的杀份。     

去甲泽拉木醛体外抑制Du-145细胞生长的初步研究

目的探讨去甲泽拉木醛对雄激素非依赖性前列腺癌细胞株Du-145的生长抑制作用及对其细胞周期改变的影响。方法分别用0、0.625、1.25、2.5、5、10、20、40μM浓度的去甲泽拉木醛作用于Du-145细胞0、24、48、72h后,以MTT法检测细胞生长活性;48h后于光镜高倍镜下观察不同浓度细胞形态学改变;24、48h后分别应用流式细胞仪检测0、1.25、10μM浓度去甲泽拉木醛作用后的细胞周期改变。结果去甲泽拉木醛对Du-145具有一定的生长抑制作用,并呈时间与浓度依赖性;细胞形态学观察发现,当药物作用48h后,随着药物作用浓度的增高,细胞逐渐呈现皱缩、变圆、脱落、碎裂、贴壁减少等现象;细胞周期分析发现,10μM作用48h后细胞中G0/G1期细胞增多,与对照组相比,差异具有统计学意义（P〈0.05）,但未出现明显凋亡峰。结论去甲泽拉木醛能显著抑制Du-145细胞的体外生长,其机制可能与将细胞阻滞在G0/G1期相关。