Key laboratory of Infection and Immunization, Department of Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Medical College, Henan University of Science and Technology, Luoyang, Henan, China.
J Cell Mol Med. 2019 Mar;23(3):1987-2000. doi: 10.1111/jcmm.14100. Epub 2018 Dec 27.
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.
米托蒽醌（MTX）耐药前列腺癌（PCa）中特异性表达基因的全球生理功能尚不清楚。本研究通过基因表达谱芯片数据分析，旨在鉴定 MTX 耐药 PCa 异种移植瘤中的差异表达基因（DEGs）。将人前列腺癌细胞系 DU145 和 PC3 在体外培养，异种移植到严重联合免疫缺陷（SCID）小鼠中，通过灌胃给予 MTX，每周 3 次，直至所有小鼠复发。对去势小鼠异种移植瘤进行 Affymetrix 人类全基因组寡核苷酸微阵列基因表达谱分析。使用 Cytoscape 软件研究蛋白质之间的关系和信号转导网络。MTX 耐药 DU145R 和 PC3R 异种移植瘤中共有 355 个重叠基因差异表达。其中，16 个基因被选择通过 qRT-PCR 在这些异种移植瘤中进行验证，并在一系列福尔马林固定、石蜡包埋和最佳切割温度（OCT）的临床肿瘤样本中进一步测试。功能和通路富集分析表明，这些 DEGs 与细胞活性、雄激素合成、DNA 损伤和修复密切相关，还涉及 ERK/MAPK、PI3K/丝氨酸-苏氨酸蛋白激酶，也称为蛋白激酶 B（PKB，AKT）和细胞凋亡信号通路。这项探索性分析提供了关于潜在候选基因的信息，并可能为 MTX 耐药 PCa 中涉及的分子级联提供新的见解。
