scholarly journals Transcription Factor HBP1 Enhances Radiosensitivity by Inducing Apoptosis in Prostate Cancer Cell Lines

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yicheng Chen ◽  
Yueping Wang ◽  
Yanlan Yu ◽  
Liwei Xu ◽  
Youyun Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Expression Level ◽  
Prostate Cancer Cells ◽  
Expression Levels ◽  
The Relationship

Radiotherapy for prostate cancer has been gradually carried out in recent years; however, acquired radioresistance often occurred in some patients after radiotherapy. HBP1 (HMG-box transcription factor 1) is a transcriptional inhibitor which could inhibit the expression of dozens of oncogenes. In our previous study, we showed that the expression level of HBP1 was closely related to prostate cancer metastasis and prognosis, but the relationship between HBP1 and radioresistance for prostate cancer is largely unknown. In this study, the clinical data of patients with prostate cancer was compared, and the positive correlation was revealed between prostate cancer brachytherapy efficacy and the expression level of HBP1 gene. Through research on prostate cancer cells in vitro, we found that HBP1 expression levels were negatively correlated with oncogene expression levels. Furthermore, HBP1 overexpression could sensitize prostate cancer cells to radiation and increase apoptosis in prostate cancer cells. In addition, animal model was employed to analyze the relationship between HBP1 gene and prostate cancer radiosensitivity in vivo; the result showed that knockdown of HBP1 gene could decrease the sensitivity to radiation of xenograft. These studies identified a specific molecular mechanism underlying prostate cancer radiosensitivity, which suggested HBP1 as a novel target in prostate cancer radiotherapy.

scholarly journals Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT

2020 ◽  
Author(s):  
Yao Zhao ◽  
Chenchen Cai ◽  
Lubing Shi ◽  
Jiwei Wang ◽  
Miaomiao Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Eph Receptor ◽  
Prostate Cancer Metastasis

Abstract Background Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is still unclear. Methods We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting. Results We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, β-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers. Conclusions These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

An in vitro model of prostate cancer bone metastasis for highly metastatic and non-metastatic prostate cancer using nanoclay bone-mimetic scaffolds

MRS Advances ◽  
2019 ◽  
Vol 4 (21) ◽  
pp. 1207-1213 ◽  
Author(s):  
MD Shahjahan Molla ◽  
Dinesh R. Katti ◽  
Kalpana S. Katti
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Metastatic Prostate Cancer ◽  
Cancer Metastasis ◽  
Human Mesenchymal Stem Cells ◽  
Culture Technique ◽  
Complex Nature ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells

ABSTRACTProstate cancer has a strong preference for metastasizing to bone which is the primary cause of prostate cancer-related morbidity and mortality. The complex nature of cancer metastasis requires the development of translational models that recapitulate a specific metastatic stage. Herein, we report the mimicking of mesenchymal to epithelial transition (MET) of prostate cancer cells using highly metastatic and a non-metastatic prostate cancer cell lines. A unique cell culture technique that we termed as ‘sequential culture’ was used to create a biomimetic bone microenvironment for metastasized prostate cancer cells by introducing bioactive factors from osteogenic induction of human mesenchymal stem cells (MSCs) within the porous 3D scaffolds. The in vitro 3D tumor model can be used as a testbed to study the interaction between prostate cancer and bone microenvironment and for the design of novel therapeutic studies.

scholarly journals CD36 promotes the epithelial–mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Min Deng ◽  
Xiaodong Cai ◽  
Ling Long ◽  
Linying Xie ◽  
Hongmei Ma ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Cd36 Expression ◽  
Cervical Cancer Cells

Abstract Background Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. Methods Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial–mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis. Results In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-β treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a–CD36 cells, suggesting that TGF-β synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-β in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-β were up-regulated in C33a–CD36 cells. These results imply that CD36 and TGF-β interact with each other to promote the EMT in cervical cancer. Conclusions Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.

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