Transcriptome analysis of differentially expressed genes and pathways associated with mitoxantrone treatment prostate cancer

Abstract

The global physiological function of specifically expressed genes of mitoxantrone (MTX)‐resistant prostate cancer (PCa) is unclear. In this study, gene expression pattern from microarray data was investigated for identifying differentially expressed genes (DEGs) in MTX‐resistant PCa xenografts. Human PCa cell lines DU145 and PC3 were cultured in vitro and xenografted into severe combined immunodeficiency (SCID) mice, treated with MTX intragastrically, three times a week until all mice relapsed. Gene expression profiles of the xenografts from castrated mice were performed with Affymetrix human whole genomic oligonucleotide microarray. The Cytoscape software was used to investigate the relationship between proteins and the signalling transduction network. A total of 355 overlapping genes were differentially expressed in MTX‐resistant DU145R and PC3R xenografts. Of these, 16 genes were selected to be validated by quantitative real‐time PCR (qRT‐PCR) in these xenografts, and further tested in a set of formalin‐fixed, paraffin‐embedded and optimal cutting temperature (OCT) clinical tumour samples. Functional and pathway enrichment analyses revealed that these DEGs were closely related to cellular activity, androgen synthesis, DNA damage and repair, also involved in the ERK/MAPK, PI3K/serine‐threonine protein kinase, also known as protein kinase B, PKB (AKT) and apoptosis signalling pathways. This exploratory analysis provides information about potential candidate genes and may bring new insights into the molecular cascade involvement in MTX‐resistant PCa.

Prognostic signatures associated with high infiltration of Tregs in bone metastatic prostate cancer

“…Androgen deprivation therapy (ADT) is the standard treatment for advanced or metastatic prostate cancer, but it progresses to castration-resistant prostate cancer (CRPC) within 2-3 years after the initiation of ADT [ 3 ]. The prognosis of men with CRPC is worse than that those who are of hormone-sensitive, and the risk of metastasis is particularly higher [ 4 , 5 ]. Patients with metastatic CRPC generally develop metastasis to the bones, which is the lethal end-stage; this poses a formidable therapeutic challenge.…”

Selective killing of homologous recombination-deficient cancer cell lines by inhibitors of the RPA:RAD52 protein-protein interaction

“…So mitoxantrone’s effects are likely attributed to multiple targets that are vital to cell survival [ 51 , 53 ]. Mitoxantrone treated cells have also shown some changes to gene expression profiles [ 57 , 58 ]. Our western analysis before and after mitoxantrone treatment show that in PEO1 cells mitoxantrone reduces RAD52 protein levels significantly, there is a significant increase in DNA damage and this synthetic lethality is part of the mechanism for the low EC 50 of 0.1 μM in PEO1 cells ( Fig 6E and 6F ).…”

Expression profile-based screening for critical genes reveals S100A4, ACKR3 and CDH1 in docetaxel-resistant prostate cancer cells

“…PCa is a heterogeneous disease that is a major health concern for men worldwide. A variety of approaches have been taken to elucidate the mechanism(s) underlying its development and to identify new therapeutic and prognostic targets [15][16][17]. Although chemotherapy is an important treatment for AIPC, its benefits are often limited by its side effects and the emergence of drug resistance.…”