Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines

2021 ◽  
Author(s):  
Ezgi Avsar Abdik ◽  
Hüseyin Abdik ◽  
Duygu Turan ◽  
Fikrettin Sahin ◽  
Martin R. Berger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Castration Resistant Prostate Cancer ◽  
Cell Type ◽  
Prostate Cancer Cell Lines ◽  
Castration Resistant ◽  
Cell Type Specific

scholarly journals Primary versus castration-resistant prostate cancer: modeling through novel murine prostate cancer cell lines

Oncotarget ◽  
2016 ◽  
Vol 7 (20) ◽  
pp. 28961-28975 ◽  
Author(s):  
Georges Daoud ◽  
Alissar Monzer ◽  
Hisham Bahmad ◽  
Farah Chamaa ◽  
Layal Hamdar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cell Lines ◽  
Castration Resistant ◽  
Cancer Modeling

scholarly journals p38 MAPK Inhibition Mitigates Hypoxia-Induced AR Signaling in Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 831
Author(s):  
Serina Cheung ◽  
Pallavi Jain ◽  
Jonathan So ◽  
Saeid Shahidi ◽  
Stephen Chung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Heat Shock ◽  
P38 Mapk ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cell Lines ◽  
Castration Resistant

Background: Aberrant androgen receptor (AR) signaling is a major driver of castration-resistant prostate cancer (CRPC). Tumor hypoxia increases AR signaling and is associated with treatment resistance in prostate cancer. Heat shock protein 27 (Hsp27) is a molecular chaperone that is activated in response to heat shock and hypoxia. Hsp27 has previously been reported to facilitate AR nuclear translocation in a p38 mitogen-activated protein kinase (MAPK) dependent manner in castration-sensitive prostate cancer cell lines. Here, we evaluated the potential for inhibiting p38 MAPK/Hsp27 mediated AR signaling under normoxia and hypoxia in experimental models of CRPC. Methods: We inhibited p38 MAPK with SB203580 in prostate cancer cell lines and measured Hsp27 phosphorylation, AR activity, cell proliferation, and clonogenicity under normoxia and hypoxia. AR activity was measured using an androgen response element driven reporter assay and qPCR to measure expression of AR target genes. Xenograft-bearing mice were treated with SB203580 to measure tumor growth and serum prostate specific antigen (PSA). Results: Our results indicate that p38 MAPK and Hsp27 are activated under normoxia and hypoxia in response to androgens in CRPC cells. p38 MAPK inhibition diminished Hsp27 activation and the hypoxia-mediated increase in AR activity. Additionally, inhibition of p38 MAPK activity decreased proliferation and survival of CRPC cells in vitro and prolonged the survival of tumor-bearing mice. Conclusions: These results suggest that p38 MAPK inhibition may represent a therapeutic strategy to disrupt AR signaling in the heterogeneous CRPC tumor microenvironment.

scholarly journals Identification of Hub Gene and Potential Drugs for Enzalutamide Resistant Castration-Resistant Prostate Cancer Depend On Bioinformatics Analysis

2021 ◽  
Author(s):  
Xi Chen ◽  
Yechen Wu ◽  
Xinan Wang ◽  
Chengdang Xu ◽  
Licheng Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cell Lines ◽  
Hub Gene ◽  
Castration Resistant

Abstract BackgroundAndrogen deprivation therapy (ADT) is still the first line method to treat PCa. However, after a period of therapy, primary PCa will inevitably progress into castration-resistant prostate cancer (CRPC). Enzalutamide (MDV3100) is an androgen receptor (AR) signal inhibitor which can delay the progression of CRPC and increase survival of patients with metastatic CRPC. However, the mechanisms of enzalutamide resistant castration-resistant prostate cancer (EnzR CRPC) are still controversial. MethodsWe collected RNA-seq data of enzalutamide resistant castration-resistant prostate cancer cell line LNCaP (EnzR LNCaP) from GSE44905, GSE78201 and GSE150807. We found hub gene from the three datasets. Then we tested the expression of hub gene in TCGA database and potential drug that has effect on hub gene. Finally, we verified the hub gene expression and drug function.ResultsFrom GSE44905, GSE78201 and GSE150807, we found 45 differently expressed genes (DEGs) between LNCaP and EnzR LNCaP. Ten hub gene were found in protein-protein interaction (PPI) network. The hub gene expression and survival analysis were analyzed by GEPIA depend on TCGA database. We found that CDK6 was highly expressed in both EnzR LNCaP cell and prostate cancer patients. Ten potential small molecules can suppress CDK6 expression from CMap. Finally, we verified the expression of CDK6 in both CRPC patients’ samples and prostate cancer cell lines. The function of three potential CDK6 inhibitors, apigenin, chrysin and fisetin, was tested in prostate cancer cell lines.ConclusionsThe study proved that the mutation of CDK6 maybe a reason to the occurrence of CRPC and suppress CDK6 expression may be a potential way in treating CRPC.

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