CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion

The mechanisms responsible for prostate cancer metastasis are incompletely understood at both the cellular and molecular levels. In this regard, chemokines are a family of small, cytokine-like proteins that induce motility of neoplastic cells, leukocytes and cancer cells. The current study evaluates the molecular mechanisms of CXCL12 and CXCR4 in prostate cancer cell migration and invasion. We report that functional CXCR4 is significantly expressed by prostate cancer cell lines, LNCaP and PC3, when compared with normal prostatic epithelial cells (PrEC). As measured using motility and invasion chamber assays, prostate cancer cells migrated and invaded through extracellular matrix components in response to CXCL12, at rates that corresponded to CXCR4 expression. Anti-CXCR4 antibodies (Abs) significantly impaired the migration and invasive potential of PC3 and LNCaP cells. CXCL12 induction also enhanced collagenase-1 (metalloproteinase-1 (MMP-1)) expression by LNCaP and PC3 cells. Collagenase-3 (MMP-13) was expressed by prostate cancer cells, but it was not expressed by PrEC cells or modulated by CXCL12. CXCL12 increased MMP-2 expression by LNCaP and PC3; however, MMP-9 expression was elevated only in PC3 cells after CXCL12-CXCR4 ligation. PC3 cells also expressed high levels of stromelysin-1 (MMP-3) after CXCL12 stimulation. CXCL12 also significantly increased stromelysin-2 (MMP-10) expression by LNCaP cells. Stromelysin-3 (MMP-11) was expressed by LNCaP cells, but not by PC3 or PrEC cells and CXCL12 induced PC3 MMP-11 expression. Membrane type-1 MMP (MMP-14) was not expressed by PrEC or LNCaP cells, but CXCL12 significantly enhanced MMP-14 expression by PC3 cells. These studies reveal important cellular and molecular mechanisms of CXCR4/CXCL12-mediated prostate cancer cell migration and invasion.     

I型膜型基质金属蛋白酶在癌细胞系中的表达及其与明胶酶A活化关系的研究

目的探讨Ｉ型膜型基质金属蛋白酶（ＭＴ１ＭＭＰ）在人肿瘤细胞系中的表达情况及其与明胶酶Ａ（ＭＭＰ２）的分泌和活化的关系。方法运用逆转录巢式ＰＣＲ、ＲＮＡ印迹分析和蛋白质印迹分析的方法,检测ＭＴ１ＭＭＰｍＲＮＡ和ＭＭＰ２蛋白在４个黑色素瘤、２个肺癌和２个前列腺癌细胞系中的表达水平。结果ＭＴ１ＭＭＰｍＲＮＡ在所有癌细胞系中均有表达,但表达水平很不一致：在４个黑色素瘤细胞系中的表达水平明显高于肺癌和前列腺癌细胞系;仅在黑色素瘤细胞系的无血清条件培养液中,检测到了活化型ＭＭＰ２,而人肺癌细胞系ＰＧ虽然分泌酶原型ＭＭＰ２,但不产生活化型ＭＭＰ２。结论ＭＴ１ＭＭＰｍＲＮＡ的表达具有一定的组织特异性,并与ＭＭＰ２的活化密切相关。     

Rho亚家族蛋白与恶性肿瘤的侵袭和转移

Rho亚家族（RhoA,RhoB,RhoC）在细胞信号转导及细胞运动中起重要作用。Rho亚家族蛋白与恶性肿瘤的侵袭与转移有密切关系,其中以RhoC的作用最显著。对Rho蛋白的深入研究有助于进一步判断其在恶性肿瘤侵袭转移中所扮演的角色,为肿瘤的治疗提供新的依据。     

Golgi phosphoprotein 3 regulates metastasis of prostate cancer via matrix metalloproteinase 9

Recent studies suggest that Golgi phosphoprotein 3 (GOLPH3) protein is a candidate metastasis gene in human cancer. The goal of this study was to determine the function of GOLPH3 in prostate cancer metastasis and to identify GOLPH3-regulated pathways and genes involved in prostate cancer metastasis. GOLPH3 expression was detected in prostate cancer. To investigate its function, PC-3 cells were stably transfected with shRNA targeting GOLPH3. Cell abilities of invasion and migration were measured in vitro. Downstream regulatory pathways of GOLPH3 were characterized using quantitative RT-PCR and Western blotting analysis. Immunohistochemical studies in prostate cancer specimens revealed a positive correlation of GOLPH3 expression with prostate cancer. GOLPH3 was expressed in prostate cancer cell lines. GOLPH3 repression resulted in the reduction of mRNA level and protein level of MMP9, accompanied with reduced phosphorylation of mTOR, EGFR and Src. Our findings suggest GOLPH3 regulate MMP9 expression which impact cell migration and invasion. This regulation is probably mediated by EGFR and Src signaling pathways.     

The use of collagen-based scaffolds to simulate prostate cancer bone metastases with potential for evaluating delivery of nanoparticulate gene therapeutics

Prostate cancer bone metastases are a leading cause of cancer-related death in men with current treatments offering only marginally improved rates of survival. Advances in the understanding of the genetic basis of prostate cancer provide the opportunity to develop gene-based medicines capable of treating metastatic disease. The aim of this work was to establish a 3D cell culture model of prostate cancer bone metastasis using collagen-based scaffolds, to characterise this model, and to assess the potential of the model to evaluate delivery of gene therapeutics designed to target bone metastases. Two prostate cancer cell lines (PC3 and LNCaP) were cultured in 2D standard culture and compared to 3D cell growth on three different collagen-based scaffolds (collagen and composites of collagen containing either glycosaminoglycan or nanohydroxyapatite). The 3D model was characterised for cell proliferation, viability and for matrix metalloproteinase (MMP) enzyme and Prostate Specific Antigen (PSA) secretion. Chemosensitivity to docetaxel treatment was assessed in 2D in comparison to 3D. Nanoparticles (NPs) containing siRNA formulated using a modified cyclodextrin were delivered to the cells on the scaffolds and gene silencing was quantified. Both prostate cancer cell lines actively infiltrated and proliferated on the scaffolds. Cell culture in 3D resulted in reduced levels of MMP1 and MMP9 secretion in PC3 cells. In contrast, LNCaP cells grown in 3D secreted elevated levels of PSA, particularly on the scaffold composed of collagen and glycosaminoglycans. Both cell lines grown in 3D displayed increased resistance to docetaxel treatment. The cyclodextrin.siRNA nanoparticles achieved cellular uptake and knocked down the endogenous GAPDH gene in the 3D model. In conclusion, development of a novel 3D cell culture model of prostate cancer bone metastasis has been initiated resulting, for the first time, in the successful delivery of gene therapeutics in a 3D in vitro model. Further enhancement of this model will help elucidate the pathogenesis of prostate cancer and also accelerate the design of effective therapies which can penetrate into the bone microenvironment for prostate cancer therapy.     

Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch‐1 signaling pathway

Prostate cancer is one of the most common malignancies in men, and it urgently demands precise interventions that target the signaling pathways implicated in its initiation, progression, and metastasis. The Notch‐1 signaling pathway is closely associated with the pathophysiology of prostate cancer. This study investigated the antitumor effects and mechanisms of curcumin, which is a well‐known natural compound from curcuminoids, in prostate cancer cells. Viability, proliferation, and migration were analyzed in two prostate cancer cell lines, DU145 and PC3, after curcumin treatment. Whether the Notch‐1 signaling pathway is involved in the antitumor effects of curcumin was examined. Curcumin inhibited the survival and proliferation of PC3 and DU145 cells in a dose‐ and time‐dependent manner and inhibited DU145 migration. Curcumin did not affect the expression of Notch‐1 or its active product NICD, but it did inhibit the expression of MT1‐MMP and MMP2 proteins in DU145 cells. We found that curcumin inhibited the DNA‐binding ability of NICD in DU145 cells. In conclusion, curcumin inhibited the survival and metastasis of prostate cancer cells via the Notch‐1 signaling pathway.     

Ⅰ型膜型基质金属蛋白酶在癌细胞系中的表达及其与明胶酶A活？…

目的 探讨Ⅰ型膜型基质金属蛋白酶在人肿瘤细胞系中的表达情况及其与明胶酶的分泌和活化的关系。方法 运用逆转录巢式ＰＣＲ,ＲＮＡ印迹分析和蛋白质印迹分析的方法,检测ＭＴ１－ＭＭＰ,ｍＲＮ和ＭＭＰ２蛋白在４个黑色素瘤,２个肺癌和２个前列腺癌细胞系中的表达水平。结果 ＭＴ１－ＭＭＰｍＲＮＡ在所有癌细胞系中均有表达,但表达水平很不一致;在４个黑色素瘤细胞系中的表达水平明显高于肺癌和前列腺癌细胞系;     

Silencing of CCR7 inhibits the growth,invasion and migration of prostate cancer cells induced by VEGFC

Early in prostate cancer development, tumor cells express vascular endothelial growth factor C (VEGF-C), a secreted molecule that is important in angiogenesis progression. CC-chemokine receptor 7 (CCR7), another protein involved in angiogenesis, is strongly expressed in most human cancers, where it activated promotes tumor growth as well as favoring tumor cell invasion and migration. The present study aimed to investigate the effect of down-regulating CCR7 expression on the growth of human prostate cancer cells stimulated by VEGFC. The CCR7-specific small interfering RNA (siRNA) plasmid vector was constructed and then transfected into prostate cancer cells. The expression of CCR7 mRNA and protein was detected by quantitative polymerase chain reaction and western blot analysis, respectively. Cell proliferation, apoptosis, cell cycle distribution and cell migration were assessed following knockdown of CCR7 by RNA interference (RNAi). Western blot analysis was used to identify differentially expressed angiogenesis- and cell cycle-associated proteins in cells with silenced CCR7. The expression levels of CCR7 in prostate cancer cells transfected with siRNA were decreased, leading to a significant inhibition of prostate cancer cell proliferation, migration and invasion induced by VEGFC. Western blot analysis revealed that silencing of CCR7 may inhibit vascular endothelial growth factor, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. In conclusion, the present study demonstrated that RNAi can effectively silence CCR7 gene expression and inhibit the growth of prostate cancer cells, which indicates that there is a potential of targeting CCR7 as a novel gene therapy approach for the treatment of prostate cancer.     

Blockade of the type I IGF receptor expression in human prostate cancer cells inhibits proliferation and invasion, up-regulates IGF binding protein-3, and suppresses MMP-2 expression

The type I insulin-like growth factor receptor (IGF-IR) is involved in tumour cell proliferation, invasion, and cancer cell survival. Several studies indicate that the IGF axis contributes to prostate cancer pathogenesis, but there is no consensus regarding the relative expression of the IGF-IR in benign and malignant prostate epithelium. In this study, endogenous IGF-IR gene expression was reduced in stably transfected PC-3 cells by employing an antisense RNA strategy which resulted in significant suppression of both PC-3 cell invasion and proliferation in vitro. Furthermore, it was demonstrated that a direct correlation exists between the inhibition of IGF-IR gene expression and either up-regulation of IGF binding protein (BP)-3 or down-regulation of matrix metalloproteinase (MMP)-2 expression in androgen-independent PC-3 cells. Moreover, inhibition of IGF-IR gene expression in transfected PC-3 cells leads to an enhanced rate of spontaneous apoptosis. In addition, expression analyses by quantitative RT-PCR on RNA from laser microdissected matched normal prostate and prostate tumour samples revealed that IGF-IR gene expression was up-regulated in nine of 12 prostate cancers, whereas IGFBP-3 gene expression was down-regulated in all 12 prostate carcinomas analysed. These results indicate an important role for IGF-IR and IGFBP-3 in the homeostasis of prostate carcinoma cells and provide a further basis for targeting IGF-IR or IGFBP-3 gene expression in order to improve understanding of the IGF-IR-activated signalling pathways and as a potential treatment for prostate cancer.     

RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development

Blood vessel formation is a complex morphological process that is only beginning to be understood at the molecular level. In this study, we demonstrate a novel and critical role for the small GTPase, RhoB, in vascular development. RhoB null mice have retarded vascular development in the retina characterized by altered sprout morphology. Moreover, pharmaceutical means to deplete RhoB in neonatal rats is associated with apoptosis in the sprouting endothelial cells of newly forming vessels. Similarly, acute depletion of RhoB by antisense or dominant-negative strategies in primary endothelial cell culture models led to apoptosis and failures in tube formation. We identified a novel link between RhoB and the Akt survival signaling pathway to explain these changes. Confocal microscopy revealed that RhoB is highly localized to the nuclear margin with a small percentage found inside the nucleus. Similarly, total Akt is throughout the cell but has increased accumulation at the nuclear margin, and active phosphorylated Akt is found primarily inside the nucleoplasm, where it partially colocalizes with the RhoB therein. We show that this colocalization is functionally relevant, because when RhoB was depleted, Akt was excluded from the nucleus and total cellular Akt protein was decreased in a proteosome-dependent manner. Because the function of RhoB in vivo appears to only be rate limiting for endothelial cell sprouting, we propose that RhoB has a novel stage-specific function to regulate endothelial cell survival during vascular development. RhoB may offer a therapeutic target in diseases such as cancer, diabetic retinopathy, and macular degeneration, where the disruption of sprouting angiogenesis would be desirable.     

RhoB loss prevents streptozotocin-induced diabetes and ameliorates diabetic complications in mice

RhoB is an early-response gene whose expression is elevated by multiple cellular stresses; this gene plays an important role in cancer, macrophage motility, and apoptosis. These factors are essential for the onset of type 1 diabetes mellitus and related complications. This study explores the role of RhoB in β-cell depletion and hyperglycemia-associated complications and tests whether the pleiotropic effect of statins on glycemic control is RhoB dependent. We induced β-cell depletion in RhoB(+/+), RhoB(+/-), and RhoB(-/-) mice with streptozotocin (STZ). Diabetic status was assessed by glucose tolerance and pancreatic islet loss. RhoB(-/-) mice showed a significant reduction in the severity of STZ-induced diabetes; only 13% of the STZ-treated RhoB-null animals became hyperglycemic, as opposed to 61% of the wild-type controls. Diabetes-related complications, such as wound healing rate and onset of nephropathy, were also assessed. Hyperglycemic RhoB(-/-) mice had fewer signs of nephropathy and showed faster wound healing than RhoB(+/+) animals. After assessing the diabetic status of mice treated simultaneously with STZ and simvastatin, we conclude that the effect of statins in improving glycemic control is RhoB independent. We propose that RhoB is a modifier of diabetes, important for the induction of β-cell loss. Suppression of RhoB expression may have potential application in the treatment of diabetes and associated complications.     

Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells.

Bone metastases are a common complication in prostate and breast cancer patients. It leads to extensive morbidity and eventually mortality. Matrix metalloproteinases (MMPs) are known to be involved in the metastatic process. MMP activity can be down-regulated by transforming growth factor beta1 (TGF-beta1), a growth-modulating factor, found in high concentrations in the bone. TGF-beta1 acts through the TGF-beta1 inhibitory element (TIE) element, a cis-acting element found in the promoter region of most MMP genes, with the exception of MMP-2. We used three human cell lines relevant for bone metastases, namely prostate adenocarcinoma PC-3, breast adenocarcinoma MDA-MB-231, and adenocarcinoma cells of unknown origin, Hs696, and one human osteosarcoma cell line, SAOS-2, and showed that in these cell lines TGF-beta1 partially lost its repressing action on MMP expression. TGF-beta1 was able to induce MMP-9 activity and protein expression in all three bone-metastatic tumour cell types, whereas MMP-9 protein levels were repressed in SAOS-2 cells. In PC-3 cells, TGF-beta1 repressed MMP-1 expression, whereas in MDA-MB-231 and SAOS-2 cells, an increase in the expression of MMP-1 protein was detected. Additionally, an increase in MMP-3 expression was observed in Hs696 cells. Expression and activity of the tissue inhibitors of matrix metalloproteinases, TIMP-1 and TIMP-2, were found increased in both PC-3 and MDA-MB-231 cells. With respect to cell proliferation, TGF-beta1 was able to induce a dose-dependent growth inhibition of up to 50% in primary human mammary epithelial cells. However, in none of the tumour cell lines was TGF-beta1 able to suppress growth substantially. Data presented in this paper support the hypothesis that TGF-beta1 can potentially disrupt the balance existing between osteoclast- and osteoblast-derived MMP activity by inducing altered expression of matrix metalloproteinases and their tissue inhibitors derived from bone-metastasizing cancer cells. This could eventually lead to skeletal destruction in patients with advanced metastatic disease.     

Cholecalciferol (Vitamin D<Subscript>3</Subscript>) Inhibits Growth and Invasion by Up-regulating Nuclear Receptors and 25-Hydroxylase (CYP27A1) in Human Prostate Cancer Cells

Epidemiological evidence suggests an inverse relationship between prostate cancer and serum vitamin D levels. We examined the ability of cholecalciferol (vitamin D₃), a calcitriol precursor, to inhibit or reverse cellular changes associated with malignant transformation and invasion and explored its mechanisms of action. The RWPE2-W99 human prostate epithelial cell line, which forms slow-growing tumors in nude mice, was used because it mimics the behavior of the majority of primary human prostate cancers. Cholecalciferol, at physiological levels: (i) inhibited anchorage-dependent and -independent growth; (ii) induced differentiation by decreasing vimentin expression with a concomitant decrease in motility/chemotaxis; (iii) decreased MMP-9 and MMP-2 activity with concomitant decrease in invasion; and (iv) exerted its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptor-α (RXR-α), and androgen receptor (AR) in a dose-dependent manner. Furthermore, we found that RWPE2-W99 prostate cancer cells, similar to RWPE-1 cells (Tokar and Webber. Clin Exp Metast 2005; 22: 265–73), constitutively express the enzyme 25-hydroxylase CYP27A1 which is markedly up-regulated by cholecalciferol. Cholecalciferol has effects similar to those of calcitriol on growth, MMP activity, and VDR. The ability of CYP27A1 to catalyze the conversion of cholecalciferol to 25(OH)D₃ and of 25(OH)D₃ to calcitriol has been reported. RWPE2-W99 cells, similar to RWPE-1 cells, appear to have the rare ability to locally convert cholecalciferol to the active hormone calcitriol. Because it can inhibit cellular changes associated with malignant transformation and invasion, we propose that cholecalciferol may be an effective agent for the treatment of prostate cancer.     

Normal and malignant prostate epithelial cells differ in their response to hepatocyte growth factor/scatter factor

Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation, differentiation, motility, and invasion of epithelial cells by binding to its cell surface receptor, the Met tyrosine kinase. In the prostate, Met is expressed predominantly by prostate epithelial cells (PrEC), whereas HGF/SF is synthesized by prostate stromal cells (PrSC). Met is also expressed in localized and metastatic prostate cancers. Our results show that PrECs in in vitro culture maintain expression of Met at a level comparable to DU145 cancer cell expression. HGF/SF secreted by PrSC stimulates tyrosine phosphorylation of the Met receptor. In normal PrEC, HGF/SF causes growth inhibition, sustained phosphorylation of mitogen-activated protein kinase, and increased CK18 expression consistent with cell differentiation. In contrast, HGF/SF significantly stimulates the proliferation of DU145 prostate cancer cells. HGF/SF in the conditioned medium of PrSC specifically induces migration of both normal and malignant prostate epithelial cells through MatriGel-coated Transwell filters. HGF/SF depletion reduces cell migration by approximately 50%. The response of PrEC is specific for HGF/SF since the other growth factors tested do not significantly affect growth or migration of PrECs. These results support the in vivo importance of the prostate stroma and specifically of HGF/SF as a unique stromal derived factor in the development and progression of prostate cancer.     

Expression of TGFβ3 and its effects on migratory and invasive behavior of prostate cancer cells: involvement of PI3-kinase/AKT signaling pathway

Transforming growth factor-β (TGFβ) is a secreted cytokine implicated as a factor in cancer cell migration and invasion. Previous studies have indicated that TGFβ isoforms may exert differential effects on cancer cells during different stages of the disease, however very little is known about the expression patterns and activity of the three isoforms in prostate cancer. Non-traditional signaling pathways including the PI3-Kinase have been associated with TGFβ-mediated effects on cancer cell invasion. In the present study, we have carried out expression analysis of TGFβ isoforms and signaling components in cell line models representing different stages of prostate cancer and studied the differential effects of specific isoforms on migratory and invasive behavior and induction of the PI3-kinase pathway. TGFβ1 and TGFβ3 were expressed in all cell lines, with TGFβ3 expression increasing in metastatic cell lines. Both TGFβ1 and TGFβ3 induced motility and invasive behavior in PC3 cells, however, TGFβ3 was significantly more potent than TGFβ1. TGFβRI and Smad3 inhibitors blocked TGFβ1 and TGFβ3 induced motility and invasion. TGFβ3 caused a significant increase in pAKT^ser473 in PC3 cells and PI3-kinase inhibitor LY294002 blocked TGFβ3 induced migration, invasion and phosphorylation of AKT. Both TGFβRI and Smad3 inhibitors blocked TGFβ3 induced pAKT^ser473. Based on these results, we conclude that TGFβ3 is expressed in metastatic prostate cancer cell lines and is involved in induction of invasive behavior in these cells. Furthermore, these effects of TGFβ3 are TGFβRI and Smad3 dependent and mediated via the PI3-kinase pathway.     

E1AF expression is associated with extra‐prostatic growth and matrix metalloproteinase‐7 expression in prostate cancer

E1AF is associated with malignant aggressiveness via regulation of matrix metalloproteinases (MMPs), which play pivotal roles in invasion through the degradation of extracellular matrix of tissues surrounding tumors. However, the clinical significance of E1AF and MMPs in patients with prostate cancer is not fully understood. We reviewed 50 tissue samples from patients with T2‐3N0M0 prostate cancer who had undergone radical operation. Expression levels of E1AF, MMP‐1, ‐3, ‐7, ‐9 and ‐14 were determined semiquantitatively by immunohistochemistry. The mean ± SD percentage of E1AF‐stained cancer cells was 8.56 ± 5.22, and it was significantly higher (p < 0.001) than the E1AF‐immunostaining index of normal cells (1.17 ± 0.61). E1AF immunostaining index in pT3 (12.74 ± 4.80) was significantly higher (p < 0.001) than that in pT2 (5.78 ± 3.31). Although E1AF expression correlated with that of MMP‐7 and MMP‐9 (r = 0.47, p < 0.001 and r = 0.41, p = 0.004, respectively), multivariate analysis showed that E1AF correlated with only MMP‐7 expression (OR = 5.81, 95% CI = 1.27–26.59, p = 0.023). Our results demonstrated that increased expression of E1AF is involved in tumor aggression of prostate cancer. This finding may be influenced by regulation of MMP‐7. We speculate that E1AF is a possible target in treatment and prevention of tumor growth in prostate cancer.     

Development of dendritic-cell based prostate cancer vaccine

Available treatments for metastatic prostate cancer have failed to demonstrate significant curative potential. Current efforts are now directed towards developments of novel strategies for the treatment of metastatic prostate cancer. Cancer immunotherapeutic strategies utilize patient immune system components to kill cancer cells. This review discusses progress in active specific immunotherapeutic approaches as potential alternative methods in the treatment of metastatic prostate cancer. One of the newest advances in cancer immunotherapy is the use of dendritic cells as the vehicle to deliver cancer antigens for an effective in vivo T cell activation. The development of dendritic cell-based prostate cancer vaccine, as well as results of several clinical trials in prostate cancer involving the administration of peptide-pulsed autologous dendritic cell pulsed are discussed.     

NEU3对人前列腺癌DU145细胞生物学行为的影响

目的:探讨神经氨酸酶3(NEU3)与人前列腺癌DU145细胞活力、侵袭和凋亡的关系,并探讨其分子机制。方法:体外培养人前列腺癌DU145细胞,并分为空白对照组和处理组,处理组再分别给予神经氨酸酶活性抑制剂DANA处理和RNA干扰靶向沉默NEU3,采用CCK-8法检测细胞的活力;Transwell法检测细胞侵袭能力;q PCR法检测2种处理方式对凋亡抑制蛋白Bcl-2 mRNA水平的影响;Western blot法检测2种处理方式对NEU3、基质金属蛋白酶2(MMP2)和Bcl-2表达的影响;流式细胞术检测细胞凋亡水平。结果:与空白对照组相比,DANA处理后前列腺癌细胞的NEU3表达无明显变化,细胞活力增强,MMP2蛋白表达减少,侵袭力减弱,凋亡无明显变化,Bcl-2的mRNA和蛋白表达减少(P 0.05);NEU3沉默后NEU3蛋白表达减少,细胞活力增强,MMP2蛋白表达和细胞侵袭力无明显变化,凋亡能力增强,Bcl-2的mRNA和蛋白表达均下降(P 0.05)。结论:抑制NEU3可以减弱人前列腺癌DU145细胞活力,增强细胞凋亡能力,但对侵袭能力无明显影响。