槲皮素通过G3BP1调控Wnt/β-catenin信号通路对前列腺癌细胞迁移、侵袭及上皮-间充质转化的影响

目的探讨槲皮素对前列腺癌(PCa)细胞迁移、侵袭及上皮-间充质转化(EMT)的影响,并分析其可能机制。方法人前列腺癌细胞(PC-3)随机分为空白对照组及槲皮素低、中、高浓度组,转染GTP酶激活蛋白-Src同源结构域3-结合蛋白1(G3BP1)siRNA及其阴性对照、pcDNA3.1-G3BP1及其阴性对照至PC-3细胞,并用槲皮素处理。分别采用细胞划痕试验和Transwell小室法检测细胞迁移、侵袭能力,实时荧光定量PCR(qRT-PCR)法检测G3BP1 mRNA表达,Western blot法检测G3BP1蛋白、EMT相关蛋白及Wnt/β-连环蛋白(β-catenin)通路蛋白表达。结果槲皮素抑制PC-3细胞迁移、侵袭,上调E-钙黏蛋白(E-cadherin)表达,下调N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)、转录因子Snail表达;槲皮素下调PC-3细胞G3BP1 mRNA和蛋白表达,下调Wnt家族成员3A(Wnt-3α)、β-catenin、磷酸化糖原合成酶激酶3β(Glycogen synthase kinase-3β,p-GSK-3β)表达,上调GSK-3β表达;沉默G3BP1增强槲皮素对PC-3细胞及Wnt/β-catenin通路的作用,过表达G3BP1逆转槲皮素对PC-3细胞及Wnt/β-catenin通路的作用。差异均有统计学意义(P<0.05)。结论槲皮素可通过抑制EMT抑制PCa细胞的迁移、侵袭能力,其作用机制可能与其靶向G3BP1抑制Wnt/β-catenin信号通路相关。     

滇重楼皂苷对前列腺癌细胞周期与凋亡的影响

目的探讨滇重楼皂苷对前列腺癌细胞增殖、周期和促凋亡的作用,以及对磷酸化CDK2表达的影响。方法使用不同浓度(0.1、0.3、1.0、3.0、10.0μmol/L)的滇重楼皂苷处理前列腺癌细胞株PC-3和Du145,应用MTT和流式细胞技术检测细胞增殖、周期分布和凋亡的改变,进一步运用免疫印迹法检测细胞周期及凋亡相关蛋白表达的改变。结果滇重楼皂苷明显抑制前列腺癌细胞株(PC-3及Du145)的增殖,使细胞在G0/G1期发生阻滞,并诱导细胞显著凋亡,抑制效果呈时间剂量梯度依赖关系;p21蛋白与Cleaved-Caspase-3表达水平明显上调,磷酸化CDK2、磷酸化RB蛋白下调。结论滇重楼皂苷增加p21蛋白水平,抑制细胞周期关键调控因子CDK2及RB的磷酸化,并且激活Caspase-3参与的细胞凋亡信号通路,从而抑制前列腺癌细胞增殖、阻断细胞周期,并诱导细胞凋亡,具有抗肿瘤活性。     

探讨抑制水通道蛋白-1在人前列腺癌细胞中的表达对癌细胞凋亡的影响

目的:通过抑制水通道蛋白-1在前列腺癌PC-3细胞的表达,了解前列腺癌细胞的凋亡情况。方法:设计合成针对前列腺癌PC-3细胞AQP1基因的小干扰RNA并构建高效表达载体,脂质体法转染PC-3细胞,Western Blot检测AQP1蛋白表达的变化。结果:AQP1在前列腺癌PC-3细胞表达,针对AQP1基因siRNA高效表达载体能够抑制AQP1蛋白在PC-3细胞的表达,AQP1蛋白相对表达量为:转染组0.54±0.04,正常对照组0.82±0.08,差异有显著性(P<0.01);成瘤实验中转染组caspase-3的含量明显高于对照组,差异显著(P<0.05),AQP1的表达量与癌细胞的凋亡呈负相关。结论:通过抑制AQP1基因的表达,有效抑制了前列腺癌PC-3细胞AQP1蛋白表达,近而使癌细胞的凋亡增加。     

Notchl参与调节胃癌顺铂耐药的机制

目的 探讨Notchl参与胃癌SGC7901/DDP细胞株顺铂耐药的机制.方法 应用Notchl通路抑制剂MW167抑制Notchl在敏感株SGC7901和耐药株SGC7901/DDP中的表达,通过噻唑蓝(MTT)比色法检测药物敏感性,流式细胞术分析细胞凋亡率,逆转录-聚合酶链反应(RTPCR)和Western blot检测敏感株SGC7901和耐药株SGC7901/DDP中Notch1和NF-kappa B(NF-κB),耐药蛋白P-糖蛋白(P-gP)的表达变化.结果 MW167抑制Notch1表达后敏感株SGC7901和耐药株SGC7901/DDP的药物敏感性显著增加,细胞凋亡率分别为23.71%和12.48%(P＜0.01),NF-κB和耐药蛋白P-gP在基因和蛋白表达水平均明显减低(P＜0.01).结论 Notch1可通过调节P-gP表达及抗凋亡信号通路参与胃癌顺铂耐药,可成为逆转胃癌耐药的新的靶点.     

三氧化二砷诱导前列腺癌PC-3细胞凋亡P_(38)信号通路的研究

目的:探讨P38信号通路在三氧化二砷(As2O3)诱导雄激素非依赖性前列腺癌PC-3细胞凋亡中的作用。方法:应用四甲基偶氮唑蓝(MTT)法检测不同浓度(0.312 5、0.625、1.25、2.5、5、10、20μmol/L)As2O3作用PC-3细胞24、48、72 h后的细胞生长抑制情况。Western印迹检测As2O3作用PC-3细胞后P38信号转导通路的表达。Annexin V/PI双染色法检测As2O3作用PC-3细胞后细胞凋亡,同时检测应用P38通路高选择抑制剂SB203580干扰P38信号通路后As2O3诱导PC-3细胞凋亡的变化。结果:As2O3诱导PC-3细胞凋亡呈现时间、剂量依赖性。As2O3可以使P38信号通路蛋白快速磷酸化,激活P38信号通路。2、10、20μmol/L As2O3作用PC-3细胞24 h后,PC-3细胞凋亡率分别为(18.9±0.43)%、(24.7±0.29)%和(49.7±1.79)%。应用P38信号通路高选择抑制剂SB203580干扰P38信号通路后,PC-3细胞凋亡率分别降低为(14.8±0.81)%、(22.1±0.51)%和(39.6±1.74)%,抑制P38信号通路可以显著降低As2O3诱导PC-3细胞的凋亡(P<0.05)。结论:P38信号通路在As2O3诱导雄激素非依赖性前列腺癌PC-3细胞凋亡中有表达,干扰P38信号通路可影响As2O3诱导PC-3细胞凋亡,提示P38信号通路参与了As2O3诱导的PC-3细胞凋亡。     

基质交联分子1对前列腺癌PC-3细胞凋亡相关蛋白表达的影响

目的:观察抑制基质交联分子1(STIM1)对前列腺癌PC-3细胞凋亡相关蛋白表达的影响。方法:将携带STIM1基因的小干扰RNA(shRNA)慢病毒载体STIM1-pGCSIL-GFP转染人激素非依赖性前列腺癌PC-3细胞,3d后荧光倒置显微镜观察转染效率;1周后RT-PCR及Western印迹验证STIM1抑制表达有效性,并采用Western印迹检测PC-3细胞中凋亡相关蛋白Bcl-2、Bax,survivin、激活型Caspase-3的表达水平。结果:倒置显微镜观察发现PC-3细胞病毒转染效率80%。转染1周后,RT-PCR及Western印迹显示STIM1被有效抑制。抑制STIM1表达后,对照组Bcl-2/Bax比率为1.24,干扰组PC-3细胞Bcl-2/Bax比率为0.31,比率显著下降;干扰组PC-3细胞survivin表达明显降低,相对表达量为对照组的0.14倍;Caspase-3裂解激活相对表达量为对照组的1.52倍(P0.05)。结论:STIM1在前列腺癌PC-3细胞中可视为致癌基因,抑制其表达可通过下调Bcl-2/Bax比率,降低survivin表达,激活Caspase-3级联通路,诱导细胞凋亡。     

靛玉红对前列腺癌PC-3细胞增殖的抑制作用

目的:研究中药成分靛玉红对雄激素非依赖性前列腺癌PC-3细胞的杀伤作用及可能的机制。方法:采用MTT方法研究靛玉红对前列腺癌PC-3细胞增殖抑制作用,采用Western印迹检测细胞周期蛋白cyclin D1及c-myc表达,采用流式细胞术检测细胞周期。结果:靛玉红降低前列腺癌细胞的存活率呈浓度依赖性,当浓度为5μmol/L时,可降低存活率至52.2%,当浓度为10μmol/L时,PC-3细胞存活率降至13.6%。靛玉红浓度为5μmol/L时可明显抑制PC-3细胞的细胞周期,结果显示G0/G1期PC-3细胞增多,而与此同时S期和G2/M期细胞减少。此外,靛玉红可以抑制细胞周期进展关键调控蛋白cyclin D1,以及与之相关Wnt信号通路的下游基因c-myc的表达。结论:靛玉红可以抑制雄激素非依赖性前列腺癌PC-3细胞的增殖,其机制可能与其抑制细胞周期以及抑制Wnt信号通路有关。     

下调盘状结构域蛋白1表达对前列腺癌PC-3细胞生物学行为的影响

目的观察下调盘状结构域蛋白1(DDR1)对前列腺癌PC-3细胞增殖、凋亡及侵袭能力的影响并探讨其可能的机制。方法采用免疫组织化学法检测前列腺组织中DDR1的表达情况。将PC-3细胞分为3组,实验组转染DDR1-shRNA重组质粒,对照组转染小干扰RNA,未转染组为正常细胞,采用四甲基偶氮唑蓝法检测细胞的增值能力,TUNEL法检测细胞的凋亡,Transwell小室检测细胞的侵袭能力变化,Western blot法检测细胞内DDR1、AKT、基质金属蛋白酶2(MMP-2)及bcl-2蛋白表达的变化。结果 DDR1蛋白的表达与前列腺癌患者的年龄、前列腺体积及总前列腺特异抗原(TPSA)无关(P0.05),与Gleason评分、淋巴结转移及分期有关(P0.05)。与未转染组及对照组相比,实验组的细胞凋亡率增高、增殖受到抑制、侵袭能力减弱,细胞内DDR1、AKT、MMP-2及bcl-2蛋白表达水平均降低。结论 DDR1蛋白表达与前列腺癌的进展相关,下调其表达可抑制前列腺癌PC-3细胞的恶性生物学行为,这可能与AKT、MMP-2及bcl-2蛋白表达的变化相关。     

国外期刊摘译

联合应用周期素依赖性蛋白激酶与AKT抑制剂诱导转移性前列腺癌细胞凋亡;肿瘤蛋白D52的表达变化对前列腺癌细胞凋亡与迁移影响的研究;抑制NF-κB与激活AP-1可增强前列腺癌细胞的凋亡;厚朴酚通过抑制EGFR／PI3K／Akt信号通路诱导人前列腺癌细胞凋亡;转移性前列腺癌细胞中PI3K／Akt依赖的转录调控与NF-κB介导的BMP-2-Smad信号通路的激活……     

重组人程序化细胞死亡5蛋白联合顺铂对前列腺癌细胞生长作用的研究

目的探讨重组人程序化细胞死亡5(rhPDCD5)联合顺铂(DDP)对人前列腺癌PC3细胞增殖和凋亡的影响及可能的机制。方法不同浓度rhPDCD5蛋白、DDP及两者联合干预PC3细胞,MTT法检测细胞增殖情况,流式细胞术检测细胞凋亡,Western blot法检测Cleaved-capase3、Bcl-xl蛋白的表达水平。结果与对照组相比,rhPDCD5、顺铂单独或联合作用PC3细胞均可抑制细胞增殖,联合用药抑制效果更显著(P0.05);rhPDCD5组、DDP组、联合用药组PC3细胞的凋亡率分别为(19.62±2.32)%、(22.45±1.57)%、(59.78±3.31)%。rhPDCD5、顺铂联合应用较单独用药可显著增强PC3细胞凋亡(P0.05);蛋白印迹法检测发现rhPDCD5组、DDP组、联合用药组中Cleaved-capase3表达明显上调,Bcl-xl表达显著下调,联合用药组效果更显著(P0.05)。结论 rhPDCD5可促进PC3细胞的凋亡,且显著增强顺铂对人前列腺癌PC3的抗癌敏感性。     

MTA1基因调控人前列腺癌PC-3细胞失巢凋亡的研究

目的:探讨MTA1基因小干扰RNA(siRNA)对前列腺癌细胞PC-3增殖和失巢凋亡的影响。方法:应用MTA1 siRNA转染处理人前列腺癌细胞系PC-3后,采用实时定量PCR和W estern印迹检测MTA1基因mRNA和蛋白水平,采用软琼脂集落培养试验检测锚着不依赖性增殖,采用琼脂糖凝胶电泳和流式细胞术检测癌细胞失巢凋亡。结果:与对照组比较,MTA1基因siRNA转染组MTA1 mRNA和蛋白水平明显下降,且呈浓度依赖性(r=0.935,P=0.0001)。MTA1 siRNA转染组软琼脂集落形成数明显减少,且与浓度相关(r=0.901,P=0.0005)。琼脂糖凝胶电泳和流式细胞术结果显示,MTA1 siRNA转染可诱导前列腺癌细胞失巢凋亡,且与浓度相关(r=0.916,P=0.0003)。结论:MTA1 siRNA可抑制人前列腺癌细胞增殖,诱导失巢凋亡是其机制之一。     

Omi/HtrA2对前列腺癌细胞的促凋亡作用

目的检测人前列腺癌细胞（PC-3M）中Omi／HtrA2的表达情况，并构建其小干扰RNA（siRNA）表达载体。探讨Omi／HtrA2对PC-3M凋亡的影响。方法以细胞免疫组织化学和逆转录-聚合酶链反应（RT-PCR）法检测Omi／HtrA2在前列腺癌细胞系（PC-3M）和正常前列腺细胞中的表达。利用软件辅助设计Omi／HtrA2特异性siRNA序列。体外合成后将其克隆入真核表达载体psiRNA-hHlneo。以脂质体法转染psiRNA-Omi／HtrA2载体至PC-3M中，以RToPCR和Western blot法检测psiRNA-Omi／HtrA2对Omi／HtrA2转录和表达的沉默效应。用噻唑蓝（MTT）比色法和流式细胞法检测siRNA导致Omi／HtrA2基因沉默后。PC-3M细胞凋亡的变化。结果细胞免疫组织化学和RT-PCR均显示Omi／HtrA2在PC3M细胞中高表达。酶切和DNA测序证实合成的siR-NA基因序列正确。并已被准确克隆入psiRNA-hHlneo载体中。psiRNA-Omi／HtrA2载体可特异性抑制PC3M细胞中Omi／HtrA2的表达。转染psiRNA-Omi／HtrA2载体的PC-3M细胞凋亡下调。结论促凋亡因子Omi／HtrA2可导致前列腺癌细胞凋亡，Omi／HtrA2的表达对前列腺癌的发展有重要作用。     

Chemokine CXCL3 mediates prostate cancer cells proliferation,migration and gene expression changes in an autocrine/paracrine fashion

Introduction

We have previously indicated that CXCL3 was upregulated in the tissues of prostate cancer, and exogenous administration of CXCL3 played a predominant role in the tumorigenicity of prostate cancer cells. In the present study, we further explored the role and the underlying mechanism of CXCL3 overexpression in the oncogenic potential of prostate cancer in an autocrine/paracrine fashion.

Methods

CXCL3-overexpressing prostate cancer cell line PC-3 and immortalized prostate stromal cell line WPMY-1 were established by gene transfection. CCK-8, transwell assays and growth of tumor xenografts were conducted to characterize the effects of CXCL3 on PC-3 cells’ proliferation and migration. Western blotting was conducted to test whether CXCL3 could affect the expression of tumorigenesis-associated genes.

Results

The results showed that CXCL3 overexpression in PC-3 cells and the PC-3 cells treated with the supernatants of CXCL3-transfected WPMY-1 cells stimulated the proliferation and migration of PC-3 cells in vitro and in a nude mouse xenograft model. Western blotting revealed higher levels of p-ERK, Akt and Bcl-2 and lower levels of Bax in the tumor xenografts transplanted with CXCL3-transfected PC-3 cells. Moreover, the tumor xenografts derived from the PC-3 cells treated with supernatants of CXCL3-transfected WPMY-1 cells showed higher expression of ERK, Akt and Bcl-2 and lower expression of Bax.

Conclusions

These findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.

     

Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro

OBJECTIVES: To evaluate synthetic small interference RNA (siRNA) compounds targeting heat-shock protein 27 (Hsp27) as an alternative approach to Hsp27 'knockdown' in prostate cancer cells, as Hsp27 expression is highly up-regulated in prostate cancer cells after androgen withdrawal or chemotherapy, to become uniformly highly expressed in androgen-independent (AI) prostate cancer. MATERIALS AND METHODS: We recently showed that targeting Hsp27 by a 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide, OGX-427, inhibits Hsp27 expression and enhances hormone- and chemotherapy in prostate cancer xenograft models. In the present study, a 'gene walk' screening different siRNAs was initially used in PC-3 and LNCaP cells to determine the most potent sequence to down-regulate Hsp27 mRNA and protein levels. The effects of Hsp27 silencing on in vitro growth rates were studied by tetrazolium-blue and crystal violet assays. Apoptosis was determined by single-stranded DNA nuclear and cleaved caspase-3 immunostaining, as well as flow cytometry. Spotted microarrays with 14,000 human oligonucleotides were used to examine changes in gene expression. RESULTS: Low concentrations of 1 nm siRNA decreased Hsp27 mRNA levels by 19-fold and suppressed protein expression to undetectable levels. Silencing of Hsp27 in prostate cancer cells by siRNA # 2 increased apoptotic rates 2.4-4 fold and caused 40-76% inhibition of cell growth in LNCaP and PC-3 cells. Characteristic cleavage of caspase-3 occurred after treatment with Hsp27 siRNA (1 nm). cDNA microarray analysis from LNCaP and PC-3 cell lines revealed differential gene expression profiles after Hsp27 down-regulation that could be used to identify various survival pathways involved in androgen-dependent and AI growth. CONCLUSIONS: These findings illustrate the potential utility of Hsp27-silencing therapy and highlight Hsp27 siRNA strategies as a novel and highly effective tool, with the potential for future targeted therapy in enhancing the efficacy of chemotherapy in advanced prostate cancer.     

ADAM17 siRNA和阿霉素联用对前列腺癌PC-3细胞增殖和凋亡的作用

目的 探讨ADAM17 siRNA联合化疗药物阿霉素（ADM）对人前列腺癌细胞株PC-3增殖和凋亡的影响。方法 用ADM处理 ADAM17 siRNA表达质粒稳定转染的PC-3细胞,采用噻唑蓝（MTT）比色法观察细胞增殖率,吖啶橙染色和流式细胞仪（FCM）检测细胞凋亡率,并对凋亡蛋白caspase-3的活性进行对比分析。结果 ADAM17 siRNA和ADM单独及联合应用均能不同程度的降低PC-3细胞增殖率,上调凋亡率。FCM检测数据显示ADAM17 siRNA和ADM单独应用的细胞凋亡率分别为（6.2±1.4）%和（17.2±1.9）%,与ADAM17 siRNA和ADM联合应用的（36.4±3.7）%相比较,差异有显著统计学意义（P<0.01）,两者在诱导caspase-3活性方面也具有良好的协同增敏作用。结论 ADAM17 siRNA和ADM对人前列腺癌PC-3均有抑制细胞增殖和促进凋亡的效果,但两者联合应用效果更好。提示分子靶向用药的基因治疗和化疗联合治疗可能是提高疗效,减少前列腺癌术后复发转移风险的重要方法。     

Role of antioxidant systems in human androgen-independent prostate cancer cells

BACKGROUND: Most prostate cancer cells respond to initial hormonal therapy; however, some of them eventually acquire resistance to the hormonal therapy. Hormone-independent prostate cancer usually exhibits resistance to chemotherapy and radiotherapy. Antioxidant systems are known to be involved in the resistance of cancer cells to chemotherapy and radiotherapy. Therefore, it is of significance to examine antioxidant systems of hormone-independent prostate cancer for enhancing the efficacy of cancer therapy. METHODS: Three cell lines of human hormone-independent prostate cancer (PC-3, PC-3 MA2, and HPC36M) were examined for activities of superoxide dismutase, catalase, and glutathione peroxidase, and for levels of protein and nonprotein thiols such as metallothionein, glutathione, and thioredoxin. Sensitivity of these cells to anticancer drugs and inducers of reactive oxygen species such as paraquat, tert-butylhydroperoxide, and hydrogen peroxide was determined by microtiter assay. RESULTS: PC-3 and PC-3 MA2, which were derived from bone metastases, were resistant to paraquat, hydrogen peroxide, and cisplatin compared with HPC36M, which was obtained from the primary prostate cancer. However, HPC36M was resistant to vinblastine compared with PC-3 and PC-3 MA2. Both PC-3 and PC-3 MA2 had higher activities of catalase and glutathione peroxidase and higher levels of glutathione and metallothionein than HPC36M. CONCLUSIONS: These data suggest that enhanced ability in scavenging free radicals by antioxidant enzymes and thiol compounds may, at least in part, contribute to the resistance of bone metastatic prostate cancer during chemotherapy.     

Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation

BACKGROUND: Bcl-2 protects cells from apoptosis and provides a survival advantage to cells over-expressing this oncogene. In addition, over expression of Bcl-2 renders cell resistant to radiation therapy. Recently, dichloroacetate (DCA) was proven to potentiate the apoptotic machinery by interacting with Bcl-2. In this study, we investigated whether treating human prostate cancer cells with DCA could modulate Bcl-2 expression and if the modulation in Bcl-2 expression could render the Bcl-2 over expressing cells more susceptible to cytotoxicity effects of radiation. METHODS: PC-3-Bcl-2 and PC-3-Neo human prostate cancer cells treated with DCA in addition to irradiation were analyzed in vitro for changes in proliferation, clonogenic survival, apoptosis, cell cycle phase distribution, mitochondrial membrane potential, and expression of Bcl-2, Bcl-xL, Bax, or Bak proteins. RESULTS: DCA alone produced significant cytotoxic effects and was associated with G1 cell cycle arrest. Furthermore, DCA was associated with an increased rate of apoptosis. The combination of DCA with irradiation sensitized both cell lines to radiation's killing effects. Treatment of PC-3-Bcl-2 or PC-3-Neo with DCA and irradiation resulted in marked changes in various members of the Bcl-2 family. In addition, DCA therapy resulted in a significant change in mitochondria membrane potential, thus supporting the notion that DCAs effect is on the mitochondria. CONCLUSIONS: This is the first study to demonstrate DCA can effectively sensitize wild-type and over expressing Bcl-2 human prostate cancer cells to radiation by modulating the expression of key members of the Bcl-2 family. Together, these findings warrant further evaluation of the combination of DCA and irradiation.     

The role of survivin and Bcl-2 in zinc-induced apoptosis in prostate cancer cells

ObjectivesTo study the effects of zinc treatment on the gene expression levels of survivin and Bcl-2 in prostate cancer cells.Materials and methodsThe effects of zinc exposure on apoptosis were assessed using two human prostate cancer cell lines, LNCaP and PC-3. Zinc-induced apoptosis was measured by Annexin V staining. The direct effect of zinc on the expression levels of zinc transporters (ZnT-1 and ZnT-4) and apoptosis-related genes (Bax, Bcl-2, and survivin) was determined by RT-PCR analysis.ResultsWhen LNCaP and PC-3 cells were exposed to various concentrations of zinc sulfate for 48 hors, their growth was inhibited in a dose-dependent manner. The levels of zinc in both cell lines treated with zinc sulfate for 24 hours were higher than in untreated cells. Exposure to zinc induced apoptosis and necrosis in LNCaP and PC-3 cells. Apoptosis became more extensive as the treatment time with zinc increased. There was a significant increase in the gene expression levels of ZnT-1 and ZnT-4 in both cell lines treated with zinc sulfate compared with untreated cells. The expression of Bax mRNA was up-regulated, while the expression of Bcl-2 and survivin were decreased in both cell lines following zinc treatment.ConclusionsExposure to zinc sulfate in human prostate cancer cells increased intracellular levels of zinc, which resulted in increased apoptosis. The apoptogenic effect of elevated concentration of zinc could be due either to increased expression of zinc transporters and increased levels of Bax or decreased Bcl-2 and survivin expression.