共查询到20条相似文献,搜索用时 21 毫秒
1.
Kasper S 《Journal of cellular physiology》2008,216(2):332-336
The cancer stem cell (CSC) model states that tumors contain a reservoir of self-renewing cells that maintain the heterogeneous cell population of the tumor. These cells appear to be resistant to therapy and can therefore survive to repopulate the tumor during progression to therapy resistant disease. The biology of CSCs is still not definitive since it is difficult to isolate them from solid tumors and analyze their characteristics in vitro. Another challenge is to correlate these characteristics with tumor development and progression in vivo. Using the prostate CSC as a model, this review presents the CSC hypothesis, reviews the origin, identification and functions of prostate CSCs, and discusses the clinical implications and therapeutic challenges CSCs have for cancer therapy. 相似文献
2.
C.-Y. Huang B. K. Velmurugan M.-C. Chen C. H. Day W.-S. Chien V. V. Padma 《Biotechnic & histochemistry》2013,88(5):374-380
ABSTRACTKHC-4 is a 2-phenyl-4-quinolone analogue that exhibits anticancer activity. Aberrant activation of β-catenin signaling contributes to prostate cancer development and progression. Therefore, targeting β-catenin expression could be a useful approach to treating prostate cancer. We found that KHC-4 can inhibit β-catenin expression and its signaling pathway in DU145 prostate cancer cells. Treatment with KHC-4 decreased total β-catenin expression and concomitantly decreased β-catenin levels in both the cytoplasm and nucleus of cells. KHC-4 treatment also inhibited β-catenin expression and that of its target proteins, PI3K, AKT, GSK3β and TBX3. We monitored the stability of β-catenin with the proteasomal inhibitor, MG132, in DU145 cells and found that MG132 reversed KHC-4-induced proteasomal β-catenin degradation. We verified CDK1/β-catenin expression in KHC-4 treated DU145 cells. We found that roscovitine treatment reversed cell proliferation by arresting the cell cycle at the G2/M phase and β-catenin expression caused by KHC-4 treatment. We suggest that KHC-4 inhibits β-catenin signaling in DU145 prostate cancer cells. 相似文献
3.
J. L. M. Krijnen P. J. A. Janssen J. A. Ruizeveld de Winter H. van Krimpen F. H. Schröder T. H. van der Kwast 《Histochemistry and cell biology》1993,100(5):393-398
The presence of androgen receptors (AR) in neuroendocrine cells was investigated in benign tissue of 10 prostatectomy specimens, in 12 prostatic adenocarcinomas with focal neuroendocrine differentiation and in 1 case of a pure neuroendocrine small cell carcinoma of the prostate. Neuroendocrine cells were defined by their reactivity with an antibody to chromogranin A. Monoclonal antibody F39.4 directed against the amino-terminal domain of the AR molecule was used to detect AR. AR and chromogranin A were simultaneously visualized with a double immunofluorescence technique. The results indicate that chromogranin positive cells in both benign and malignant prostatic tissue lack detectable expression of AR. No effect of endocrine therapy was noted. These results are in agreement with the hypothesis that prostatic neuroendocrine tumour cells represent an androgen insensitive cell population, which incidentally may expand to replace the androgen-sensitive tumour cell population during androgen ablation therapy. 相似文献
4.
NRP-154 is a tumorigenic epithelial cell line derived from the preneoplastic dorsal-lateral prostate of rats. These cells are exquisitely sensitive to TGF-β induced apoptosis. In contrast, we find that NRP-154 cells can sustain overexpression of exogenous Bax protein, which is different from non-tumor cells where Bax functions as a ubiquitous stimulator of apoptosis. NRP-154 cells stably overexpressing Bax show increased sensitivity to TGF-β induced apoptosis. The degree of TGF-β induced apoptosis displays high correlation with cleavage of Bax at the amino-terminus. Our data indicate that prostate cancer cells can host high levels of latent Bax which can be activated through post-translational modification. 相似文献
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Wang FL Qin WJ Wen WH Tian F Song B Zhang Q Lee C Zhong WD Guo YL Wang H 《Cancer immunology, immunotherapy : CII》2007,56(11):1785-1793
Dendritic cells (DCs) are highly potent initiators of the immune response, but DC effector functions are often inhibited by
immunosuppressants such as transforming growth factor beta (TGF-β). The present study was conducted to develop a treatment
strategy for prostate cancer using a TGF-β-insensitive DC vaccine. Tumor lysate-pulsed DCs were rendered TGF-β insensitive
by dominant-negative TGF-β type II receptor (TβRIIDN), leading to the blockade of TGF-β signals to members of the Smad family,
which are the principal cytoplasmic intermediates involved in the transduction of signals from TGF-β receptors to the nucleus.
Expression of TβRIIDN did not affect the phenotype of transduced DCs. Phosphorylated Smad-2 was undetectable and expression
of surface co-stimulatory molecules (CD80/CD86) were upregulated in TβRIIDN DCs after antigen and TGF-β1 stimulation. Vaccination
of C57BL/6 tumor-bearing mice with the TβRIIDN DC vaccine induced potent tumor-specific cytotoxic T lymphocyte responses against
TRAMP-C2 tumors, increased serum IFN-γ and IL-12 level, inhibited tumor growth and increased mouse survival. Furthermore,
complete tumor regression occurred in two vaccinated mice. These results demonstrate that blocking TGF-β signals in DC enhances
the efficacy of DC-based vaccines.
Fu
-Li Wang, Wei-Jun Qin contributed equally to this report. 相似文献
7.
α-Tocopheryl succinate is one of the most effective analogues of vitamin E for inhibiting cell proliferation and inducing cell death in a variety of cancerous cell lines while sparing normal cells or tissues. αTocopheryl succinate inhibits oxidative phosphorylation at the level of mitochondrial complexes I and II, thus enhancing reactive oxygen species generation which, in turn, induces the expression of Nrf2-driven antioxidant/detoxifying genes. The cytoprotective role of Nrf2 downstream genes/proteins prompted us to investigate whether and how α-tocopheryl succinate increases resistance of PC3 prostate cancer cells to pro-oxidant damage. A 4 h α-tocopheryl succinate pre-treatment increases glutathione intracellular content, indicating that the vitamin E derivative is capable of training the cells to react to an oxidative insult. We found that α-tocopheryl succinate pre-treatment does not enhance paraquat-/hydroquinone-induced cytotoxicity whereas it exhibits an additional/synergistic effect on H2O2-/docetaxel-induced cytotoxicity. 相似文献
8.
Transfection efficiency of the novel reagent metafectene has not been compared with that of lipofectamine in the published
English literature. We used these agents to transfect two prostate cancer cell lines, PC3 and Gsα, with a deoxyribonucleic acid (DNA) expression vector that generates double-stranded ribonucleic acid (RNA) for RNA interference
(RNAi). Cotransfection of the green fluorescent protein (GFP) reporter gene revealed that the mean (± standard deviation)
transfection efficiencies with lipofectamine were 5.8±0.4% for PC3 cells and 3.6±1.5% for Gsα cells. Mean transfection efficiency with metafectene declined to 0.1±0% for PC3 cells but improved to 54.6±5.5% for Gsα cells. With Gsα cells, metafectene transfection of GFP plasmid alone yielded 46.9% positive cells, and cotransfection with CD44v9 expression
vector yielded 45.9% positive cells. The visual impact of the transfected RNAi construct was detectable at the protein level
4 to 6 d posttransfection and was more dramatic after using metafectene than after using lipofectamine. Thus, in vitro, metafectene
transfection efficiency was sufficient to allow us to assess the functional significance of our RNAi construct, suggesting
metafectene as an excellent candidate for RNAi-mediated anticancer gene therapy. 相似文献
9.
Huang JK Chou CT Chang HT Shu SS Kuo CC Tsai JY Liao WC Wang JL Lin KL Lu YC Chen IS Liu SI Ho CM Jan CR 《Journal of receptor and signal transduction research》2011,31(3):247-255
Effect of the carcinogen thapsigargin on human prostate cancer cells is unclear. This study examined if thapsigargin altered basal [Ca2?](i) levels in suspended PC3 human prostate cancer cells by using fura-2 as a Ca2?-sensitive fluorescent probe. Thapsigargin at concentrations between 10?nM and 10 μM increased [Ca2?](i) in a concentration-dependent fashion. The Ca2? signal was reduced partly by removing extracellular Ca2? indicating that Ca2? entry and release both contributed to the [Ca2?](i) rise. This Ca2? influx was inhibited by suppression of phospholipase A2, but not by inhibition of store-operated Ca2? channels or by modulation of protein kinase C activity. In Ca2?-free medium, pretreatment with the endoplasmic reticulum Ca2? pump inhibitor 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) nearly abolished thapsigargin-induced Ca2? release. Conversely, pretreatment with thapsigargin greatly reduced BHQ-induced [Ca2?](i) rise, suggesting that thapsigargin released Ca2? from the endoplasmic reticulum. Inhibition of phospholipase C did not change thapsigargin-induced [Ca2?](i) rise. At concentrations of 1-10 μM, thapsigargin induced cell death that was partly reversed by chelation of Ca2? with BAPTA/AM. Annexin V/propidium iodide staining data suggest that apoptosis was partly responsible for thapsigargin-induced cell death. Together, in PC3 human prostate cancer cells, thapsigargin induced [Ca2?](i) rises by causing phospholipase C-independent Ca2? release from the endoplasmic reticulum and Ca2? influx via phospholipase A2-sensitive Ca2? channels. Thapsigargin also induced cell death via Ca2?-dependent pathways and Ca2?-independent apoptotic pathways. 相似文献
10.
Dunning NL Laversin SA Miles AK Rees RC 《Cancer immunology, immunotherapy : CII》2011,60(8):1181-1193
Cancer stem cells have been implicated in a number of solid malignancies including prostate cancer. In the case of localised
prostate cancer, patients are often treated with surgery (radical prostatectomy) and/or radiotherapy. However, disease recurrence
is an issue in about 30% of patients, who will then go on to receive hormone ablation therapy. Hormone ablation therapy is
often palliative in a vast proportion of individuals, and for hormone-refractory patients, there are several immunotherapies
targeting a number of prostate tumour antigens which are currently in development. However, clinical responses in this setting
are inconsistent, and it is believed that the failure to achieve full and permanent tumour eradication is due to a small,
resistant population of cells known as ‘cancer stem cells’ (CSCs). The stochastic and clonal evolution models are among several
models used to describe cancer development. The general consensus is that cancer may arise in any cell as a result of genetic
mutations in oncogenes and tumour suppressor genes, which consequently result in uncontrolled cell growth. The cancer stem
cell theory, however, challenges previous opinion and proposes that like normal tissues, tumours are hierarchical and only
the rare subpopulation of cells at the top of the hierarchy possess the biological properties required to initiate tumourigenesis.
Furthermore, where most cancer models infer that every cell within a tumour is equally malignant, i.e. equally capable of
reconstituting new tumours, the cancer stem cell theory suggests that only the rare cancer stem cell component possess tumour-initiating
capabilities. Hence, according to this model, cancer stem cells are implicated in both tumour initiation and progression.
In recent years, the role of epithelial–mesenchymal transition (EMT) in the advancement of prostate cancer has become apparent.
Therefore, CSCs and EMT are both likely to play critical roles in prostate cancer tumourigenesis. This review summarises the
current immunotherapeutic strategies targeting prostate tumour antigens taking into account the need to consider treatments
that target cancer stem cells and cells involved in epithelial–mesenchymal transition. 相似文献
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Hui-Jung Jung Jong-Wook Park Jason S. Lee Byeong-Churl Jang Min-Ho Suh 《Biochemical and biophysical research communications》2009,390(1):71-502
Silibinin is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) and is reported to exhibit anticancer properties. Recently, it has been reported that silibinin inhibits hypoxia-inducible factor-1α (HIF-1α) expression in cancer cells. However, the precise mechanism by which silibinin decreases HIF-1 expression is not fully understood. In this study, silibinin inhibited basal and hypoxia induced expression levels of HIF-1α protein in LNCaP and PC-3 prostate cancer cells, while the rate of HIF-1α protein degradation and mRNA levels were not affected. We found that the decrease in HIF-1 protein by silibinin correlated with suppression of de novo synthesis of HIF-1α protein. Silibinin inhibited global protein synthesis coincided with reduction of eIF4F complex formation and induction of phosphorylation of the translation initiation factor 2α (eIF-2α) which can cause inhibition of general protein synthesis. These results suggest that silibinin’s activity to inhibit HIF-1α protein expression is associated with the suppression of global protein translation. 相似文献
13.
Chun Hei Antonio Cheung Xueying Sun Jagat R Kanwar Ji-Zhong Bai LiTing Cheng Geoffrey W Krissansen 《Cancer cell international》2010,10(1):1-11
Background
Survivin is a member of the inhibitor-of-apoptosis (IAP) family which is widely expressed by many different cancers. Overexpression of survivin is associated with drug resistance in cancer cells, and reduced patient survival after chemotherapy and radiotherapy. Agents that antagonize the function of survivin hold promise for treating many forms of cancer. The purpose of this study was to investigate whether a cell-permeable dominant-negative survivin protein would demonstrate bioactivity against prostate and cervical cancer cells grown in three dimensional culture.Results
A dominant-negative survivin (C84A) protein fused to the cell penetrating peptide poly-arginine (R9) was expressed in E. coli and purified by affinity chromatography. Western blot analysis revealed that dNSurR9-C84A penetrated into 3D-cultured HeLa and DU145 cancer cells, and a cell viability assay revealed it induced cancer cell death. It increased the activities of caspase-9 and caspase-3, and rendered DU145 cells sensitive to TNF-α via by a mechanism involving activation of caspase-8.Conclusions
The results demonstrate that antagonism of survivin function triggers the apoptosis of prostate and cervical cancer cells grown in 3D culture. It renders cancer cells sensitive to the proapoptotic affects of TNF-α, suggesting that survivin blocks the extrinsic pathway of apoptosis. Combination of the biologically active dNSurR9-C84A protein or other survivin antagonists with TNF-α therapy warrants consideration as an approach to cancer therapy. 相似文献14.
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16.
Hong Chen Hai-Xiang Shen Yi-Wei Lin Ye-Qing Mao Li-Ping Xie 《Cell cycle (Georgetown, Tex.)》2018,17(13):1602-1613
Small RNAs play an important role in gene regulatory networks. The gene suppressive effect of small RNAs was previously the dominant focus of studies, but during the recent decade, small RNA-induced gene activation has been reported and has become a notable gene manipulation technique. In this study, a putative tumor suppressor, INTS6, was activated by introducing a promoter-targeted small RNA (dsRNA-915) into castration-resistant prostate cancer (CRPC) cells. Unique dynamics associated with the gene upregulation phenomenon was observed. Following gene activation, cell proliferation and motility were suppressed in vitro. Downregulation of Wnt/β-catenin signaling was observed during the activation period, and the impairment of β-catenin degradation reversed the tumor suppressor effects of INTS6. These results suggest the potential application of small activating RNAs in targeted gene therapy for CRPC. 相似文献
17.
U.K. Misra 《Biochemical and biophysical research communications》2010,391(1):272-1259
Antibodies against the COOH-terminal domain of cell surface GRP78 induce apoptosis in cancer cell lines via activation of p53 signaling. We now have studied the effects of PFT-α, an inhibitor of p53-mediated apoptotic pathways, on anti-GRP78 antibody-induced activation of p53 and pro-apoptotic signaling in 1-LN prostate cancer cells. Pretreatment of 1-LN cancer cells with this agent significantly inhibited antibody or doxorubicin-induced upregulation of p53. Concomitantly, PFT-α treatment prevented down regulation of ERK1/2 activation by either antibody or doxorubicin. Likewise, PFT-α prevented increases in the pro-apoptotic proteins BAD, BAK, BAX, PUMA, and NOXA as well as activation of caspases-3, -7, and -9. We conclude that antibody-induced apoptosis in prostate cancer cells is mediated predominantly by p53 using the mitochondrial pathway of apoptosis. 相似文献
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19.
The role of bone morphogenetic proteins in the progression and metastasis of prostate cancer is a topic that has undergone extensive research. This study investigates the role of BMP member growth and differentiation factor 9 (GDF-9) in the progression of this disease. GDF-9 was over-expressed and knocked-down in PC-3 cells, respectively. Furthermore, along with the use of a generated recombinant GDF-9 protein, these cells were then analyzed for any changes in their invasiveness and expression of epithelial-mesenchymal transition (EMT) associated genes. GDF-9 was shown to promote the invasiveness of PC-3 cells together with an induction in the expression of genes including SNAI1, RhoC, ROCK-1, and N-cadherin, while reducing levels of E-cadherin. These expression changes are characteristic of the onset of EMT, and resulted in the cells having a more mesenchymal-like morphology. Treating these cells with activin-like kinase-5 (ALK-5) inhibitor, demonstrated that GDF-9 induced up-regulation of these molecules was ALK-5 dependant. This study shows that in PC-3 cells, GDF-9 signaling via ALK-5, can promote cell invasiveness via a complex network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancer cells. 相似文献
20.
Huong PT Moon DO Kim SO Kim KE Jeong SJ Lee KW Lee KS Jang JH Erikson RL Ahn JS Kim BY 《Cellular signalling》2011,23(5):857-865
Although endoplasmic reticulum (ER) stress induction by some anticancer drugs can lead to apoptotic death of cancer cells, combination therapy with other chemicals would be much more efficient. It has been reported that proteasome inhibitors could induce cancer cell death through ER-stress. Our study, however, showed a differential mechanism of proteasome inhibitor-I (Pro-I)-induced cell death. Pro-I significantly enhanced apoptotic death of PC3 prostate cancer cells pretreated with tunicamycin (TM) while other signaling inhibitors against p38, mitogen activated kinase (MEK) and phosphatidyl-inositol 3-kinase (PI3K) did not, as evidenced by cell proliferation and cell cycle analyses. NF-κB inhibition by Pro-I, without direct effect on ER-stress, was found to be responsible for the TM-induced chemosensitization of PC3 cells. Moreover, TM-induced/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression was enhanced by Pro-I without change in GRP78 expression. CHOP knockdown by siRNA also showed a significant decrease in Pro-I chemosensitization. All these data suggest that although TM could induce both NF-κB activation and CHOP expression through ER-stress, both NF-κB inhibition and increased CHOP level by Pro-I are required for enhanced chemosensitization of PC3 prostate cancer cells. Thus, our study might contribute to the identification of anticancer targets against prostate cancer cells. 相似文献