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