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1.
Aim of Work: Here, we examined the role of resveratrol as a radiosensitizer by targeting cancer stem cells in radioresistant prostate cancer cells (PC-3) using stem cell markers CD44, CD49b and CD29, SOX2, OCT4, CXCR4, DCLK1 and EMT markers such as VIM and E-cadherin. Material and Methods: This study was an in vitro study involving PC-3 cell line which was dividing into four groups. Group I (CO): Control group composed of cells grown in the same medium without treatment with ionizing radiation or resveratrol. Group II (IR): Cells were treated with ionizing radiation alone. Group III (RV): Cells were treated with resveratrol alone. Group VI (IR&RV): The cells were treated with ionizing radiation and resveratrol in combination. The viability of cells was assessed by MTT assay. Genes of interest were measured by RT-PCR and the radiosensitizing efficacy of RV on proliferating cancer cells was determined by clonogenic assay. Results: Ionizing radiation significantly reduced PC-3 viability, lowered stem cell markers and affected epithelial to mesenchymal transition (EMT) genes expression at all doses (2, 4, 6 and 8 Gray). Resveratrol significantly decreased PC-3 viability and lowered stem cell markers and EMT genes expression at concentrations 35, 70 and 140 µM. Combining resveratrol treatment with ionizing radiation leads to significant reduction in cell viability and stem cell markers genes which was noticed with increasing the radiation dose when compared to ionizing radiation alone treated group. Conclusion: Resveratrol has a radiosensitizing effect, that ability is triggered by reducing the expression of cancer stem cell markers and affecting EMT markers. Resveratrol showed to be a good candidate for further studies as anticancer drug in the treatment of human prostate cancer.  相似文献   

2.
The Role of Cell Motility in Prostate Cancer   总被引:2,自引:0,他引:2  
Cell motility is a critical determinant of prostate cancer metastasis. The current review discusses the role for cell motility in metastatic dissemination, the evidence that prostate cancer metastasis is dependent on increased cell motility and describes the molecules whose expression has been shown to correlate with the increased motility that accompanies prostate cancer progression. These include receptors for growth factors and cytokines that regulate cell motility as well as intracellular proteins that interact with actin or that regulate signal transduction associated with cell motility. Motility related modulators include both positive regulators of cell movement that are upregulated during tumor progression and suppressors of cell movement that are down-regulated during progression. Because altered expression of such genes may determine the metastatic potential of any particular prostate tumor, we conclude that the appearance or disappearance of motility-related molecules could be used to aid in the diagnosis and prognosis of human prostate cancer.  相似文献   

3.
Prostate cancer is the second most common cancer in men. Prostate-specific antigen (PSA) levels, commonly used in the diagnosis of prostate cancer, are increased in both malign and benign conditions, such as prostate hyperplasia (BPH) and prostatitis. Thus, more specific markers are urgently needed to discriminate between prostate cancer and benign diseases of the prostate. The purpose of this study is to examine both the intracellular and extracellular free amino acid profiles of metastatic prostate cancer cells (PC-3), normal prostate cells (PNT-1A), and metabolic changes (e.g., pH). In this study, cancer and normal cells were incubated in the appropriate medium. Then, the cells were collected and lysed in a cold medium. Finally, intracellular and extracellular free amino acid profiles were analyzed using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Extracellular metabolites were analyzed via blood gas measurements, including pH, CO2, and O2. We determined that intracellular prostate cancer cells include high amounts of glutamic acid, aspartic acid, glutamine, alpha aminobutyric acid, glycine, and proline, while cancer cells mostly use hydroxyproline, serine, alpha aminobutyric acid, ethanolamine, and valine from the extracellular medium. It was also determined that the extracellular pH of cancer cells is more acidic than that of normal cells, and normal cells have higher levels of Ca+, Cl-, and Glu. In this study, we found that group amino acids have significant potential in prostate cancer pathogenesis; therefore, they have potential usefulness as a biomarker in the diagnosis of prostate cancer.  相似文献   

4.
Quercetin is one of the most abundant dietary flavonoids widely present in many fruits and vegetables. Previousin vitro studies has shown that quercetin acts as an antioxidant and anti-inflammatory agent and it has potentanticarcinogenic properties as an apoptosis inducer. In this study we examined apoptotic effects of quercetin onthe K562 erythroleukemia cell line. K562 cells were induced to undergo apoptosis by hydrogen peroxide. Cellviability and apoptosis level were assessed by annexin V and PI staining methods using flow cytometry. Viabilityof K562 cells was increased by low dose of quercetin (5-100 μM) for 3 hours. High doses of quercetin provedtoxic (100-500 μM, 24 hours) and resulted in decrease of K562 cell viability as expected (p<0.01). As to results,100 μM quercetin was defined as a protective dose. Also, K562 cell apoptosis due to hydrogen peroxide wasdecreased in a dose dependent manner. As indicated in previous studies, reduction of superoxides by free radicalscavengers like quercetin could be beneficial for prevention of cancer but consumption of such flavonoids duringcancer treatment may weaken effects of chemotherapeutics and radiotherapy. Especially cancer patients shouldbe carefully considered for traditional phytotherapy during cancer treatment, which can lead to controversialresults.  相似文献   

5.
Polyphenolic compounds from pomegranate fruit extracts (PFEs) have been reported to possessantiproliferative, pro-apoptotic, anti-inflammatory and anti-invasion effects in prostate and other cancers.However, the mechanisms responsible for the inhibition of cancer invasion remain to be clarified. In thepresent study, we investigated anti-invasive effects of ellagic acid (EA) in androgen-independent human(PC-3) and rat (PLS10) prostate cancer cell lines in vitro. The results indicated that non-toxic concentrationsof EA significantly inhibited the motility and invasion of cells examined in migration and invasion assays.The EA treatment slightly decreased secretion of matrix metalloproteinase (MMP)-2 but not MMP-9 fromboth cell lines. We further found that EA significantly reduced proteolytic activity of collagenase/gelatinasesecreted from the PLS-10 cell line. Collagenase IV activity was also concentration-dependently inhibited byEA. These results demonstrated that EA has an ability to inhibit invasive potential of prostate cancer cellsthrough action on protease activity.  相似文献   

6.
刘妍  左树森  徐勇  张志宏 《中国肿瘤》2013,22(4):317-320
[目的]探讨尿液中前列腺癌基因-3(prostate cell antigen 3,PCA3)对前列腺癌的诊断价值.[方法]收集119例前列腺癌(prostate cancer,PCa)患者和207例前列腺增生(benign prostatic hyperplasia,BPH)患者前列腺按摩后尿液,采用反转录聚合酶链反应技术,分析PCA3基因在PCa和BPH患者尿液中的表达情况,并与血中前列腺特异性抗原(prostate specific of antigen,PSA)进行应用价值的比较.[结果]尿PCA3 mRNA阳性104例,其中PCa100例、BPH 4例.尿PCA3 mRNA诊断PCa的敏感度、特异性、准确率、阳性预测值(PPV)、阴性预测值(NPV)、阳性似然比(+LR)、阴性似然比(-LR)分别为84.03%、98.07%、92.94%、96.15%、91.44%、43.49、0.16;血PSA诊断PCa的检出率为48.92%(113/231),明显低于尿PCA3 mRNA诊断PCa的检出率96.15%(100/104),差异有统计学意义(P<0.01).此外,PSA位于灰色区域4~10ng/ml77例,病理结果显示PCa 8例,BPH 69例,PCa检出率10.39%;尿PCA3 mRNA阳性7例,其中PCa 6例、BPH 1例,PCa检出率85.71%;尿PCA3 mRNA诊断PCa的敏感度和特异性分别为75.00%和98.55%.[结论]与血PSA相比,尿PCA3 mRNA诊断PCa敏感度稍低,但具有很好的特异性和阳性预测值,对于首次活检阴性而尿PCA3 mRNA阳性的患者意义重大,提示可能需要重复穿刺活检.在PSA介于灰色区域4~10ng/ml时,穿刺结果阳性率较低(10.39%),尿PCA3 mRNA诊断PCa的特异性达98.55%,可协助判断是否需要穿刺活检.  相似文献   

7.
For a study of interactions between the cancer-associated fibroblasts (CAFs) and the putative prostate cancer stem cells (CSCs), we used a conditional Pten deletion mouse model of prostatic adenocarcinoma to isolate both CAF cultures and CSC-enriched cell fractions from the primary tumors. The CSC subpopulation exhibited a collective phenotype of Lin(-)/SCA-1(hi)/CD49f(hi)/p63(hi)/CK5(hi)/AR(lo)/CK18(lo)/Survivin(hi)/Runx2(hi) and contained cells with the ability to both self-renew and differentiate into basal and luminal cells in vitro. The spheroids generated from the CSC-enriched subpopulation mimicked the glandular structures that could be produced from a similarly isolated cell fraction from the normal mouse prostate. The efficiency of spheroid formation was found to be influenced differentially by the nature of the fibroblasts that were co-cultured in the 3-D system. The growth and differentiation properties of the CSCs were significantly more enhanced by factors released from CAFs relative to normal prostate fibroblasts (NPFs). Additionally, increased commitment to differentiation to the luminal cell lineage was noted when CAFs were present. When CSCs admixed with either CAFs or NPFs were examined for formation of prostatic glandular structures in renal grafts in vivo, the lesions formed were generally more in numbers in the presence of CAFs than NPFs. Furthermore, lesions formed with CAFs often displayed tumor-like complex histopathology and contained increased numbers of proliferating cells. Taken together, the results suggested that the CAFs in the prostate tumor microenvironment can contribute to the biologic properties of the CSCs and by this account may play a major role in prostate tumorigenesis and progression. Thus, it would be important now to identify the paracrine and/or juxtacrine factors that are responsible for the stimulation of the cancer stem cells.  相似文献   

8.
9.
Stem Cell Genes in Androgen-independent Prostate Cancer   总被引:1,自引:0,他引:1  
Despite recent advances in the detection and treatment of early stage prostate cancer, there remains little effective therapy for patients with locally advanced and/or metastatic disease. Although the majority of patients with advanced disease respond initially to androgen ablation therapy, most go on to develop androgen-independent tumors that are inevitably fatal. Therefore, understanding the mechanisms by which a hormone-sensitive tumor escapes hormonal control is critical to the development of effective therapeutic modalities. The study of the differentiation pathways of normal and abnormal prostate growth has led to the development of a stem cell model for prostate cancer [1–3]. Recent work discussed in this commentary suggests that prostate tumors resist apoptosis and proliferate by adopting features of normal prostatic stem/progenitor cells. Basal cells, the putative stem/progenitor cells of the prostate, possess the phenotype of androgen-independence as do most advanced prostate cancers. Therefore, the study of basal cells may prove critical to understanding prostate carcinogenesis and to the development of novel strategies for preventing and managing prostate cancer.  相似文献   

10.
Circulating bone marrow-derived Mesenchymal Stem Cells (BM-MSCs) have an innate tropism for tumor tissue in response to the inflammatory microenvironment present in malignant lesions. The prostate is bombarded by numerous infectious & inflammatory insults over a lifetime. Chronic inflammation is associated with CXCL12, CCL5, and CCL2, which are highly overexpressed in prostate cancer. Among other cell types, these chemoattractant stimuli recruit BM-MSCs to the tumor. MSCs are minimally defined as plastic-adhering cells characterized by the expression of CD90, CD73, and CD105 in the absence of hematopoietic markers, which can differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs are immunoprivileged and have been implicated in tumorigenesis through multiple mechanisms, including promoting proliferation, angiogenesis, and metastasis, in addition to the generation of an immunosuppressive microenvironment. We have demonstrated that MSCs represent 0.01-1.1% of the total cells present in core biopsies from primary human prostatectomies. Importantly, these analyses were performed on samples prior to expansion in tissue culture. MSCs in these prostatectomy samples are FAP-, CD90-, CD73-, and CD105-positive, and CD14-, CD20-, CD34-, CD45-, and HLA-DR-negative. Additionally, like BM-MSCs, these prostate cancer-derived stromal cells (PrCSCs) were shown to differentiate into osteoblasts, adipocytes, & chondrocytes. In contrast to primary prostate cancer-derived epithelial cells, fluorescently-labeled PrCSCs & BM-MSCs were both shown to home to CWR22RH prostate cancer xenografts following IV injection. These studies demonstrate that not only are MSCs present in sites of prostate cancer where they may contribute to carcinogenesis, but these cells may also potentially be used to deliver cytotoxic or imaging agents for therapeutic and/or diagnostic purposes.  相似文献   

11.
Inflammatory conditions increase the risk of cancer. Strong evidences showed that inflammation contributes to breast cancer and prostate cancer in different ways such as inflammationinduced DNA or RNA damage, overexpression cytokines, chemokines etc. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. Some possible mechanisms by which inflammation can contribute to carcinogenesis have been found. These mechanisms by which inflammation contributes to cancer give broader views of cancer development. These insights are fostering new antiinflammatory therapeutic approaches to cancer development.  相似文献   

12.
Teriflunomide (TFN) is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS) generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN''s apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization) and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention.  相似文献   

13.

PURPOSE

Upregulation of Bcl-2 family members is a well-established mechanism in the development of androgen-independent prostate cancer. Inhibition of the antiapoptotic proteins Bcl-2 and Mcl-1 may delay the transition to androgen-independent growth.

EXPERIMENTAL DESIGN

We have established a prostate cancer model with VCaP prostate cancer cells in vivo to study the transition to androgen independence. Here, we investigated the efficacy of AT-101 (R-(-)-gossypol acetic acid; a pan small molecule inhibitor of Bcl-2, Bcl-xL, and Mcl-1) in combination with surgical castration to delay the onset of androgen-independent growth in vivo.

RESULTS

AT-101 (15 mg/kg, per os (p.o.) 5 days/week) in combination with surgical castration delayed the onset of androgen-independent prostate cancer growth in vivo. In addition, we demonstrate the induction of caspase-9-and caspase-3-dependent induction of apoptosis following AT-101 treatment in vitro which was accompanied by an AT-101-induced downregulation of Bcl-2 and Mcl-1 mRNA and protein expression.

CONCLUSIONS

We conclude that AT-101 in combination with surgical castration delays the onset of androgen-independent prostate cancer in vivo by disrupting the antiapoptotic activity of Bcl-2 upregulation during the transition to androgen independence. Further studies are needed to define the mechanism of action by which AT-101 attenuates the expression of Bcl-2 and Mcl-1 and to characterize the potential for AT-101 in combination with hormone therapy.  相似文献   

14.
Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.  相似文献   

15.
 目的 研究生长抑素类似物奥曲肽对胃癌细胞株SGC790 1细胞的增殖、蛋白激酶B及端粒酶活性的影响。方法 应用奥曲肽作用于胃癌细胞株SGC790 1细胞不同时间后 ,检测其对体外培养胃癌细胞的抑制率 ,胃癌细胞蛋白激酶B(Akt/PKB)及端粒酶的活性。结果 奥曲肽对胃癌细胞增殖有明显抑制作用 ,呈剂量依赖性。同时能显著抑制胃癌细胞Akt/PKB的活性和端粒酶的活性 (12 ,2 4 ,4 8h均P <0 .0 1)。结论 生长抑素对胃癌细胞株SGC790 1细胞增殖有抑制作用 ,其机制与抑制Akt/PKB及端粒酶活性有关。  相似文献   

16.
Better understanding of the distinct and redundant functions of the proprotein convertase (PC) enzyme family within pathophysiological states has a great importance for potential therapeutic strategies. In this study, we investigated the functional redundancy of PCs in prostate cancer in the commonly used androgen-sensitive LNCaP and the androgen-independent DU145 human cell lines. Using a lentiviral-based shRNA delivery system, we examined in vitro and in vivo cell proliferation characteristics of knockdown cell lines for the endogenous PCs furin, PACE4, and PC7 in both cell lines. Of the three PCs, only PACE4 was essential to maintain a high-proliferative status, as determined in vitro using XTT proliferation assays and in vivo using tumor xenografts in nude mice. Furin knockdowns in both cell lines had no effects on cell proliferation or tumor xenograft growth. Paradoxically, PC7 knockdowns reduced in vitro cellular proliferation but had no effect in vivo. Because PCs act within secretion pathways, we showed that conditioned media derived from PACE4 knockdown cells had very poor cell growth-stimulating effects in vitro. Immunohistochemistry of PACE4 knockdown tumors revealed reduced Ki67 and higher p27KIP levels (proliferation and cell cycle arrest markers, respectively). Interestingly, we determined that the epidermal growth factor receptor signaling pathway was activated in PC7 knockdown tumors only, providing some explanations of the paradoxical effects of PC7 silencing in prostate cancer cell lines. We conclude that PACE4 has a distinct role in maintaining proliferation and tumor progression in prostate cancer and this positions PACE4 as a relevant therapeutic target for this disease.  相似文献   

17.

Purpose of Review

It is now accepted that prostate cancer has a low alpha/beta ratio, establishing a strong basis for hypofractionation of prostate radiotherapy. This review focuses on the rationale for hypofractionation and presents the evidence base for establishing moderate hypofractionation for localised disease as the new standard of care. The emerging evidence for extreme hypofractionation in managing localized and oligometastatic prostate cancer is reviewed.

Recent Findings

The 5-year efficacy and toxicity outcomes from four phase III studies have been published within the last 12 months. These studies randomizing over 6000 patients to conventional fractionation (1.8–2.0 Gy per fraction) or moderate hypofractionation (3.0–3.4 Gy per fraction). They demonstrate hypofractionation to be non-inferior to conventional fractionation.

Summary

Moderate hypofractionation for localized prostate cancer is safe and effective. There is a growing body of evidence in support of extreme hypofractionation for localized prostate cancer. Extreme hypofractionation may have a role in managing prostate oligometastases, but further studies are needed.
  相似文献   

18.
卢文  杨艳梅  马敬全 《中国肿瘤》2016,25(7):553-558
[目的]分析自噬在熊果酸抑制人宫颈癌HeLa细胞增殖中的作用.[方法]体外培养人宫颈癌HeLa细胞,不同浓度(5、10、20μmol/L)的熊果酸处理48h后,采用MTT法检测HeLa细胞增殖抑制率的变化;透射电镜观察细胞自噬超微结构的改变;Western blotting检测自噬相关蛋白p62及Beclin-1的表达情况;微管相关蛋白1轻链3A/B (microtubule-associated protein 1 light chain 3 A/B,LC3A/B)免疫荧光检测熊果酸对HeLa细胞自噬水平的影响;检测自噬抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)抑制自噬前后对熊果酸增殖抑制作用的影响.[结果]不同浓度(5、10、20 μmol/L)的熊果酸处理组对HeLa细胞的抑制率分别为20.1%±1.3%、35.6%±2.6%和49.0%±1.0%,熊果酸可抑制HeLa细胞增殖并呈剂量依赖性(=446.177,P<0.001);熊果酸能诱导HeLa细胞发生自噬:透射电镜观察发现经熊果酸处理后HeLa细胞中自噬囊泡明显增加;Western blotting分析表明熊果酸可呈剂量依赖性增加Beclin-1的表达,降低p62的表达;免疫荧光检测显示熊果酸处理后,HeLa细胞的荧光强度与对照组相比明显增强;3-MA与熊果酸联合作用于HeLa细胞时可抑制细胞增殖.[结论]熊果酸抑制HeLa细胞增殖,并诱导其发生自噬,自噬抑制剂3-MA能够增强熊果酸对HeLa细胞的增殖抑制作用.  相似文献   

19.
目的研究Bcl-xL基因特异性RNA干扰对前列腺癌PC-3细胞株体外增殖能力和凋亡的影响。方法构建靶向Bcl-xL的小干扰RNA(siRNA)表达载体,转染PC-3细胞后,采用半定量RT-PCR和Western blot法检测转染前后Bcl-xL mRNA及蛋白表达水平的改变;采用噻唑兰(MTT)法检测细胞生长增殖情况;TUNEL试剂盒测定细胞的凋亡情况。结果靶向Bcl-xL的序列特异性的siRNA可以有效地抑制PC-3细胞Bcl-xL基因的表达。转染靶向Bcl-xL的siRNA表达质粒可以显著抑制PC-3细胞的增殖(P<0.001),诱导细胞凋亡(P<0.001)。结论Bcl-xL基因特异性RNA干扰可以显著抑制前列腺癌PC-3细胞的体外增殖并诱导细胞凋亡。  相似文献   

20.
目的从miR-199a-3p在前列腺癌高、低转移潜能细胞中的表达差异出发,研究其在高转移前列腺癌细胞株1E8细胞运动转移中的作用及可能的分子机制。方法运用Realtime PCR法检测 miR-199a-3p在前列腺癌高、低转移潜能配对细胞系中的表达差异。通过划痕实验及transwell实验观察1E8细胞及转染 miR-199a -3p mimics及mimics NC后该细胞运动迁移能力的变化。结果(1)Realtime PCR结果显示高转移潜能1E8细胞中miR-199a-3p表达水平明显低于低转移潜能2B4细胞。(2)上调miR-199a-3p会减弱1E8细胞的运动转移能力。结论miR-199a-3p的上调可以抑制前列腺癌细胞的运动迁移能力。  相似文献   

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