Zyflamend, a combination of herbal extracts, attenuates tumor growth in murine xenograft models of prostate cancer

Prostate cancer (PrC) is the second deadliest cancer of males in the United States Hormone deprivation therapy (HDT), a common therapy for advanced forms of the disease, results in tumor regression; unfortunately, tumors inevitably become castrate-resistant. Diet is not an appropriate primary therapy for refractory forms of the disease; however, diet may be effective as an adjuvant to HDT, potentially extending the latency period and delaying relapse and/or inhibiting refractory growth. Zyflamend? is a combination of extracts from multiple herbs, each with reported anticancer properties. Zyflamend can inhibit growth of various PrC cell lines, but no studies have investigated its potential use in vivo using a model of castrate-resistant PrC. In this study, oral doses of Zyflamend at human equivalent doses inhibited androgen-dependent and castrate-resistant tumor growth in a mouse model that mimics advanced stages of the disease, and reduced the expression of a number of biomarkers linked to PrC progression including pAKT, prostate specific antigen, histone deacetylases, and androgen receptor. In summary, this is the first article to report that Zyflamend, when provided at human equivalent doses, can potentiate the effects of hormone deprivation on tumor regression and growth inhibition of androgen-dependent and castrate-resistant PrC tumors in vivo.     

Zyflamend reduces the expression of androgen receptor in a model of castrate-resistant prostate cancer

Prostate cancer is the most commonly diagnosed solid malignancy, and tumor cells eventually transform to castrate resistance through multiple pathways including activation of the androgen receptor via insulin-like growth factor receptor (IGF-1R) signaling involving phospho-AKT (pAKT). In this study, a mixture of herbal extracts, Zyflamend?, was used as a treatment in a model of castrate-resistant prostate cancer using CWR22Rv1 cells. Zyflamend reduced androgen receptor and IGF-1R expression along with a reduction of IGF-1-mediated proliferation of CWR22Rv1 cells. IGF-1 induced downstream AKT phosphorylation; however, the induction of pAKT was not associated with androgen receptor expression. Further, constitutively active form of AKT had no effect on nuclear expression of androgen receptor, indicating that upregulation of pAKT did not promote androgen receptor expression or nuclear translocation in castrate-resistant CWR22Rv1 cells. Conversely, Zyflamend reduced androgen receptor expression following IGF-1 stimulation and in cells overexpressing pAKT. These results demonstrated that Zyflamend inhibited IGF-1-stimulated cell growth, IGF-1R expression, and androgen receptor expression and its nuclear localization, but these effects were not dependent upon phosphatidylinositol 3-kinase/pAKT signaling. In conclusion, Zyflamend decreased cell proliferation and inhibited IGF-1R and androgen receptor expression in a phosphatidylinositol 3-kinase/pAKT independent manner.     

沉默信息调节因子1小干扰RNA诱导前列腺癌细胞PC3细胞凋亡

摘要:目的　观察沉默信息调节因子1（SIRT1）小干扰RNA（siRNA）对前列腺癌细胞PC3细胞生长增殖、DNA合成、细胞凋亡和Bcl-2和Bax蛋白的表达变化,探讨SIRT1在前列腺癌发生中的可能机制。方法　体外培养PC3细胞,分空白对照组（mock组）,转染阴性对照组（scramble siRNA组）和SIRT1 siRNA转染组;Western blot检测PC3细胞中SIRT1的干涉效能;MTT法测定PC3细胞的增殖率;BrdU掺入法测定DNA合成;流式细胞术检测细胞凋亡;Western blot检测PC3细胞中细胞凋亡关键调控因子Bcl-2和Bax的蛋白表达。结果　与对照组比较,SIRT1 siRNA组SIRT1蛋白表达降低（P＜0.01）,PC3细胞的增殖和DNA合成明显受抑制（P＜0.01）,细胞凋亡比例增加（P＜0.01）,Bcl-2蛋白表达减少,Bax的表达增加。结论　下调SIRT1的表达抑制细胞增殖和DNA合成,诱导前列腺癌PC3细胞发生凋亡,其机制可能与改变细胞凋亡关键调控因子Bcl-2和Bax的蛋白表达相关。     

曲古抑菌素A阻断Stat3信号通路诱导前列腺癌细胞凋亡的实验研究

目的本实验研究组蛋白去乙酰化酶抑制剂曲古抑菌素A(TSA)对前列腺癌细胞DU145的抑制作用及其对信号传导与转录激活因子3(Stat3)信号通路的影响。方法采用不同浓度的TSA处理DU145不同时间后,四氮甲基唑蓝比色法测定TSA对细胞活力的抑制效应;流式细胞仪分析细胞周期的改变;蛋白印迹实验检测细胞凋亡相关蛋白半胱氨酸蛋白酶(Caspase)家族的Caspase-8、Caspase-9、Caspase-3、二磷酸腺苷核糖多聚酶(PARP)及Stat3信号蛋白活性(phospho-Stat3)的变化。结果 TSA时间和剂量依赖性地抑制DU145细胞的增殖,TSA处理细胞24 h和48 h后,细胞生存率分别是85.7%和68.7%;细胞经TSA处理后,细胞形态和细胞周期均发生明显的变化,细胞周期被阻断在G0/G1期,其细胞百分比从55.6%增加到68.5%;Western blot检测结果显示,TSA作用DU145细胞后,Stat3信号蛋白的磷酸化水平下降,同时IL-6对Stat3的刺激诱导作用也被TSA所阻断;Caspase-8、Caspase-9、Caspase-3、PARP等凋亡蛋白被TSA诱导活化,并发生显著剪切。结论 TSA能够通过抑制Stat3信号通路的活性来诱导DU145细胞凋亡。     

姜黄素对人宫颈癌SiHa细胞株增殖、凋亡和COX-2表达的影响

目的:体外研究中药姜黄素(Cur)对子宫颈癌SiHa细胞的增殖抑制和诱导凋亡的作用及与环氧合酶(COX-2)表达的关系。方法:以不同浓度的姜黄素(10～30μmol/L),分12～72 h四个时间点处理SiHa细胞,光镜观察细胞形态变化;用四甲基偶氮唑蓝(MTT)法测定细胞增殖抑制率;用DNA梯状电泳(DNA ladder)检测凋亡的发生;Western blot检测COX-2蛋白的表达;用放射免疫法检测细胞PGE2释放水平。结果:姜黄素可抑制SiHa细胞增殖,作用呈明显的时效和量效关系,差异有统计学意义(P<0.01);姜黄素可诱导SiHa细胞凋亡,DNA ladder呈梯状条带;姜黄素可明显抑制COX-2的表达,差异有统计学意义(P<0.01),并呈浓度依赖性;姜黄素明显抑制SiHa细胞PGE2释放水平,差异有统计学意义(P<0.01)。结论:姜黄素体外对SiHa细胞具有增殖抑制作用和促进凋亡作用,其机制可能与抑制COX-2蛋白表达、降低PGE2释放水平有关。     

Comparison of nonselective cyclo-oxygenase (COX) inhibitor and selective COX-2 inhibitors on preimplantation loss, postimplantation loss and duration of gestation: an experimental study

Comparison of effect of three cyclo-oxygenase (COX) inhibitors, indomethacin, nimesulide and celecoxib, on the following were assessed: preimplantation loss, postimplantation loss and duration of gestation in Wistar rats. Indomethacin (2.5 and 10 mg/kg), nimesulide (10 and 40 mg/kg) and celecoxib (10 and 40 mg/kg) were administered by gavage daily from days 1-7 for preimplantation loss studies and from day 13 to completion of gestation for postimplantation and duration of gestation studies. Number of animals in each group was six. Preimplantation loss was calculated by subtracting number of implantation sites from number of luteal spots and postimplantation loss was calculated by noting the difference between implantation sites and pups delivered. The higher doses of the three drugs were shown to increase significantly the preimplantation loss, while all the doses of three drugs produced a significant increase in postimplantation loss. Number of animals crossing upper limit of 23-day normal gestation period in Wistar rats was increased in the higher doses. At comparable dose levels, there was no significant difference among the three drugs.     

Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products

Zyflamend, a polyherbal preparation, was designed based on constituents that exhibit antiproliferative, antiinflammatory, antioxidant, antiangiogenic, and apoptotic activities through a mechanism that is not well defined. Because the nuclear factor (NF)-kappaB has been shown to regulate proliferation, invasion, and metastasis of tumor cells, we postulated that Zyflamend modulates the activity of NF-kappa B. To test this hypothesis, we examined the effect of this preparation on NF-kappaB and NF-kappaB-regulated gene products. We found that Zyflamend inhibited receptor activator of NF-kappa B ligand-induced osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of which are known to require NF-kappa B activation. Zyflamend suppressed NF-kappa B activation induced by both TNF and cigarette smoke condensate. The expression of NF-kappa B-regulated gene products involved in antiapoptosis (inhibitor-of-apoptosis protein 1/2, Bcl-2, Bcl-xL, FADD-like interleukin-1betaconverting enzyme/caspase-8 inhibitory protein, TNF receptor-associated factor-1, and survivin) and angiogenesis (vascular endothelial growth factor, cyclooxygenase-2, intercellular adhesion molecule, and matrix metalloproteinase-9) was also down-regulated by Zyflamend. This correlated with potentiation of cell death induced by TNF and chemotherapeutic agents. Overall, our results indicate that Zyflamend suppresses osteoclastogenesis, inhibits invasion, and potentiates cytotoxicity through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.     

Influence of genistein isoflavone on matrix metalloproteinase-2 expression in prostate cancer cells

We investigated the expression of matrix metalloproteinase (MMP)-2 in human LNCaP and PC3 prostate cancer cell lines in response to genistein exposure. Initially we studied the phytosensitivity of the cells to genistein using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to determine percentage cell viability/inhibition and the terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end-labeling apoptosis assay to assess the type of cell death. The results revealed that genistein inhibited growth and proliferation in both PC3 (hormone-dependent) and LNCaP (hormone-independent) prostate cancer cell lines, that there was no significant difference in sensitivity to genistein between PC3 and LNCaP cells, and that the effect of genistein on the cells was dose- and time-dependent. The results also revealed that inhibition of cell growth in both PC3 and LNCaP cells was predominantly due to apoptotic cell death. These results were consistent with data in previous studies. This was followed by determination of the MMP-2 profile in response to genistein treatment. The results indicated a significant dose- and time-dependent inhibition of MMP-2 expression levels in both cells, with a highly significant negative correlation between MMP-2 levels and concentration of genistein. This is of phytotherapeutic significance in view of the pivotal role of MMP-2 expression in the pathogenesis of prostate cancer. Increasing expression of MMPs has been identified in many human cancers, including prostate cancer. Our findings indicate that genistein could be a potent therapeutic inhibitor of MMP-2 in line with current concepts of targeted treatment.     

COX-2、Ki-67与乳腺癌新辅助化疗疗效的关系

目的 研究COX-2、Ki-67在乳腺癌新辅助化疗前后的表达变化及其与新辅助化疗疗效的关系.方法 应用免疫组织化学法检测48例乳腺癌新辅助化疗前后标本中COX-2、Ki-67的表达.结果 新辅助化疗总有效率为70.8%,总临床获益率为95.8%.化疗前后COX-2阳性率、Ki-67指数变化显著,分别由化疗前的62.5%和(46.81±23.17)%,降到化疗后的41.7%和(33.23±18.11)%,P<0.05.化疗前后COX-2阳性的乳腺癌组织中Ki-67指数均显著高于COX-2阴性者,P<0.01.新辅助化疗后COX-2表达阳性者,化疗效果差(P<0.05);而Ki-67高表达者总有效率高于低表达者(P<0.05).结论 COX-2、Ki-67可作为指导乳腺癌新辅助化疗并预测化疗敏感性的分子生物学指标.     

Therapeutic vaccination with dendritic cells pulsed with tumor-derived Hsp70 and a COX-2 inhibitor induces protective immunity against B16 melanoma

Prophylactic immunization of mice with autologous tumor-derived heat shock proteins (Hsp) generates effective anti-tumor immunity. However, this approach is ineffective when used therapeutically, partly due to the immunosuppressive effects of the growing tumor. Here we sought to overcome this problem by therapeutic vaccination with dendritic cells (DC) pulsed with Hsp70 and a COX-2 inhibitor. We found that Hsp70 induces IL-6 and IL-10 production and suppressed expression of CD40 on DC. Incubation of DC with tumor-conditioned medium attenuated Hsp70-induced expression of CD80 and induced expression of COX-2. Inhibition of COX-2 partially reversed the stimulatory effect of Hsp70 on DC IL-6 and IL-10 production and enhanced expression of CD80 and MHC classes I and II. Therapeutic administration of DC pulsed in vitro with Hsp70 in the presence of a COX-2 inhibitor significantly reduced progression of B16 tumors in mice and significantly enhanced survival. This was associated with a reduction in the frequency of IL-10-producing CD4(+) T cells and enhancement of IFN-gamma-producing CD8(+) T cells. Our findings provide a novel immunotherapeutic approach against cancer based on attenuation of COX-2-mediated immunosuppression using in vitro modulated DC.     

Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells

High consumption of soy isoflavones in Asian diets has been correlated with a lower incidence of clinically important cases of prostate cancer. The chemopreventive properties of these diets may result from an interaction of several types of isoflavones, including genistein and daidzein. The present study investigated the effects of a soy isoflavone concentrate (ISF) on growth and gene expression profiles of PC-3 human prostate cancer cells. Trypan blue exclusion and [3H]-thymidine incorporation assays showed that ISF decreased cell viability and caused a dose-dependent inhibition of DNA synthesis, respectively, with 50% inhibition (IC50) of DNA synthesis at 52 mg/L (P = 0.05). The glucoside conjugates of genistein and daidzein in ISF were converted to bioactive free aglycones in cell culture in association with the inhibition of DNA synthesis. Flow cytometry and Western immunoblot analyses showed that ISF at 200 mg/L caused an accumulation of cells in the G2/M phase of the cell cycle (P < 0.05) and decreased cyclin A by 20% (P < 0.05), respectively. The effect of ISF on the gene expression profile of PC-3 cells was analyzed using Affymetrix oligonucleotide DNA microarrays that interrogate approximately 17,000 human genes. Of the 75 genes altered by ISF, 28 were upregulated and 47 were downregulated (P < 0.05). Further analysis showed that IL-8, matrix metalloproteinase 13, inhibin beta A, follistatin, and fibronectin mRNA levels were significantly reduced, whereas the expression of p21(CIP1), a major cell cycle inhibitory protein, was increased. The effects of ISF on the expression of IL-8 and p21(CIP1) mRNA and protein were validated at high and low ISF concentrations. Our data show that ISF inhibits the growth of PC-3 cells through modulation of cell cycle progression and the expression of genes involved in cell cycle regulation, metastasis, and angiogenesis.     

RNA干扰对卵巢癌细胞mTOR表达及细胞增殖与凋亡的影响

目的:探讨RNA干扰技术对人卵巢癌细胞SKOV3中mTOR的表达及对细胞增殖与凋亡的影响。方法:培养SKOV3细胞系,设计合成mTOR siRNA实验分4组:正常培养组:未转染的正常培养SKOV3细胞;空白对照组:转染空脂质体的SKOV3细胞;转染组:转染mTOR siRNA的SKOV3细胞;无义对照组:转染无义siRNA的SKOV3细胞。采用Western blot法检测各组细胞中的mTOR蛋白表达水平;应用MTT法检测细胞增殖;流式细胞仪检测细胞凋亡。结果:mTOR siRNA转染组SK-OV3细胞mTOR蛋白的表达显著低于各对照组(P<0.05);mTOR siRNA转染组SKOV3细胞增殖低于各对照组(P<0.05);mTOR siRNA转染组细胞凋亡率高于各对照组(P<0.05)。结论:mTOR siRNA对SKOV3细胞中mTOR蛋白的表达有明显的抑制作用,特异性阻断mTOR基因表达可显著抑制SKOV3细胞的增殖并促进其凋亡。     

Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells

Increased soy consumption in Asian diets, resulting in increased serum isoflavone levels, has been associated with a decreased risk for prostate adenocarcinoma (PCa). The isoflavone genistein is believed to be the anticancer agent found in soy, and significant levels of genistein have been detected in human prostatic fluid, implicating the role of genistein in PCa prevention. Recent studies have demonstrated genistein's ability to inhibit cell growth and induce apoptosis in several cell lines; however, the molecular mechanisms of genistein's effect are not known. We have evaluated the mechanism by which genistein may inhibit PCa cell growth. Here we report that genistein inhibits PCa cell growth in culture in a dose-dependent manner, which is accompanied by a G2/M cell cycle arrest. Cell growth inhibition was observed with concomitant downregulation of cyclin B, upregulation of the p21WAF1 growth-inhibitory protein, and induction of apoptosis. Collectively, these results provide experimental evidence for a novel effect of genistein on cell cycle gene regulation, resulting in the inhibition of cell growth and ultimate demise of tumor cells.     

Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells

Sulforaphane (SFN) is a major isothiocyanate compound in cruciferous vegetables such as broccoli, cauliflower, and Brussels sprouts. Preclinical animal models have recently shown that SFN and other isothiocyanates may be useful for prostrate cancer (PCa) chemoprevention. In this study we used a DU145 human PCa cell culture model to investigate the role of protein kinase signaling pathway(s) in SFN-induced cell cycle arrest and apoptosis and whether another chemopreventive agent selenium enhances the apoptosis potency of SFN. The results showed that SFN exposure for 24 h or longer significantly decreased the number of viable DU145 cells in a dose-dependent manner with an IC50 of asymptotically equal to 10 microM. The decreased cell number was associated with G2/M phase arrest and apoptotic cell death, with the latter being evidenced by caspase-mediated cleavage of poly(ADP-ribose) polymerase and increased release of histone-associated DNA fragments. A peptide inhibitor of caspase-8 completely blocked SFN-induced apoptosis and that for caspase-9 exerted a major protection; however, neither inhibitor attenuated SFN-induced G2/M arrest. Regarding potential mediators, SFN treatment induced a transient rise of reactive oxygen species (ROS) peaking within (1/2) h and the activation of JNK within 1 h but did not have any detectable effect on the phosphorylation of p38MAPK or ERK1/2 from 6 h to 24 h. Pretreatment of cells with N-acetylcysteine to enrich intracellular glutathione blocked SFN-induced ROS and apoptotic cell death. Inhibiting the JNK activity with a pharmacologic inhibitor SP600125 abolished the induction of G2/M arrest and apoptosis by SFN, whereas chemical inhibitors for p38MAPK and MEK1/2 did not have any modulating effect on SFN-induced apoptosis. Taken together, the data indicate that SFN decreased viable DU145 cell number in large part through the generation of ROS and JNK-mediated signaling to G2/M arrest and caspase-dependent apoptosis. Selenium in the form of inorganic sodium selenite salt or methylseleninic acid did not enhance SFN-induced apoptosis in this cell culture model.     

结直肠癌Hp感染与COX-2和G-17及PINP的关系

目的分析结直肠癌患者幽门螺杆菌(Hp)感染与环氧合酶-2(COX-2)、胃泌素17(G-17)、I型胶原氨基端前肽(PINP)的关系。方法选取2017年2月-2019年10月三所医院行结肠镜检查及外科手术切除的结直肠癌患者230例(结直肠癌组)、同期结肠镜检查阴性健康体检者100名(对照组),采用13C尿素呼气试验检测Hp感染情况,采用免疫组织化学染色法、放射免疫分析法、双抗体夹心酶联免疫吸附试验测定COX-2、G-17、PINP水平,分析Hp感染与临床特征、COX-2、G-17、PINP的关系。结果结直肠癌组Hp感染率70.43%高于对照组30.00%(P<0.001);Hp感染与结直肠癌患者肿瘤部位、TNM分期、淋巴结转移有关(P<0.05);结直肠癌组、对照组中,Hp阳性患者G-17水平高于Hp阴性患者,Hp阳性患者PINP水平低于Hp阴性患者(P<0.05),结直肠癌组中Hp阳性患者COX-2阳性率高于Hp阴性患者(P<0.05)。结论结直肠癌患者Hp感染发生率高,且与COX-2、G-17、PINP水平有关,四者可能共同作用参与结直肠癌的发生发展,应予以监测。     

Diallyl disulphide, a beneficial component of garlic oil, causes a redistribution of cell-cycle growth phases, induces apoptosis, and enhances butyrate-induced apoptosis in colorectal adenocarcinoma cells (HT-29)

Colon cancer is a leading and expanding cause of death worldwide. A major contributory factor to this disease is diet composition; some components are beneficial (e.g, dietary fiber), whereas others are detrimental (e.g., alcohol). Garlic oil is a prominent dietary constituent that prevents the development of colorectal cancer. This effect is believed to be mainly due to diallyl disulphide (DADS), which selectively induces redox stress in cancerous (rather than normal) cells that leads to apoptotic cell death. However, the detailed mechanism by which DADS causes apoptosis remains unclear. We show that DADS treatment of colonic adenocarcinoma cells (HT-29) initiates a cascade of molecular events characteristic of apoptosis. These include a decrease in cellular proliferation, translocation of phosphatidylserine to the plasma-membrane outer-layer, activation of caspase-3 and -9, genomic DNA fragmentation, and G(2)/M phase cell-cycle arrest. Short-chain fatty acids (SCFAs), particularly butyrate (abundantly produced in the gut by bacterial fermentation of dietary polysaccharides), enhance colonic cell integrity but, in contrast, inhibit colonic cancer cell growth. Combining DADS with butyrate augmented the apoptotic effect of butyrate on HT-29 cells. These results suggest that the anticancerous properties of DADS afford greater benefit when supplied with other favorable dietary factors (short chain fatty acids/polysaccharides) that likewise reduce colonic tumor development.     

人参皂苷Rh2联合顺铂对人卵巢癌SKOV-3细胞凋亡的影响

目的:探讨人参皂苷Rh2联合顺铂对于人卵巢癌细胞株SKOV-3的影响。方法:采用MTT比色法检测人参皂苷Rh2与DDP联合应用对SKOV-3细胞株增殖的影响,利用流式细胞仪分析细胞周期及凋亡情况,并计算细胞平均凋亡率,利用Western-blot技术观察SKOV-3细胞内HER-2蛋白的表达。结果:①Rh2与DDP联合应用分别作用于SKOV-3卵巢癌细胞株,单独应用DDP 350μmol/L和600μmol/L IC50降为DDP 250μmol/L和300μmol/L。②流式细胞术检测显示,DDP+Rh2组凋亡率在SKOV-3细胞系中为32.2%,SKOV-3细胞被阻止于G1期,在SKOV-3 DDP细胞中为12.5%,均显著高于仅应用DDP组细胞(P<0.05),SKOV-3 DDP细胞亦被阻止于G1期。③Western blotting结果显示,SKOV-3细胞中DDP+Rh2组HER-2蛋白表达较对照组、DDP组、Rh2组显著降低(P<0.05)。结论:人参皂苷Rh2与DDP联合应用对SKOV-3卵巢癌细胞株有促凋亡作用,并改善卵巢癌细胞株SKOV-3 DDP对DDP的敏感性。     

Momilactone B, an allelochemical of rice hulls, induces apoptosis on human lymphoma cells (Jurkat) in a micromolar concentration

Although momilactone B has been studied as an allelochemical of rice (Oryza sativa L.), to date we have no report showing the effect of momilactone B on mammalian cells. This study was undertaken to examine whether this allelochemical has anticancer activity on cancer cells. We show here that momilactone B at micromolar doses has antitumor efficacy by inducing apoptosis in several blood cancer cells including human leukemic T cells. In addition, our study elucidated that anticancer activity of momilactone B on human leukemic T cells resulted from the induction of apoptosis via caspase and mitochondria. From these results, momilactone B can be considered as a novel therapeutic strategy for human leukemic T cells from its direct apoptosis-inducing activity.     

氢醌对人白血病细胞凋亡及相关蛋白Bcl-2、Bax及Caspase-3表达的影响

目的 研究氢醌对白血病细胞株U937细胞凋亡及相关蛋白Bcl-2、Bax及Caspase-3表达的影响。方法 用不同浓度的氢醌处理U937细胞24 h、48 h后,采用MTT法来检测细胞增殖抑制率;经瑞-吉染色后,观察细胞形态变化;采用流式细胞仪检测细胞凋亡;采用免疫印迹法检测Bcl-2、Bax及Caspase-3蛋白表达。结果 (1)U937细胞的增殖抑制率随氢醌作用时间及浓度的增加而增加,呈时间-剂量依赖性(P<0.05);(2)氢醌作用后,部分细胞体积增大,胞浆中有空泡,胞核发生畸形;(3)流式细胞术结果显示,细胞凋亡率随着氢醌作用时间及浓度的增加而增加,呈时间-剂量依赖性(P<0.05);(4)免疫印迹结果显示,与空白组相比较,染毒48h时,细胞Bax蛋白的表达量增加(P<0.05),而Bcl-2蛋白表达量减少(P<0.05),Bcl-2/Bax比值下降(P<0.05),染毒24 h时,细胞Caspase-3蛋白的表达量增加(P<0.05);与染毒24 h各组相比较,染毒48 h时细胞Caspase-3蛋白的表达量随时间延长呈增加趋势(P<0.05)。结论 氢醌可以诱导U937细胞凋亡,其机制可能与调控凋亡相关蛋白Bcl-2、Bax及Caspase-3的表达有关。