PDF(Pubmed)
Abstract：
Cisplatin, a powerful chemotherapy medication, has long been a cornerstone in the fight against cancer due to chemotherapeutic failure. The mechanism of cisplatin resistance/failure is a multifaceted and complex issue that consists mainly of apoptosis inhibition through autophagy sensitization. Currently, researchers are exploring ways to regulate autophagy in order to tip the balance in favor of effective chemotherapy. Based on this notion, the current study primarily identifies the differentially expressed genes (DEGs) in cisplatin-treated autophagic ACHN cells through the Illumina Hi-seq platform. A protein-protein interaction network was constructed using the STRING database and KEGG. GO classifiers were implicated to identify genes and their participating biological pathways. ClueGO, David, and MCODE detected ontological enrichment and sub-networking. The network topology was further examined using 12 different algorithms to identify top-ranked hub genes through the Cytoscape plugin Cytohubba to identify potential targets, which established profound drug efficacy under an autophagic environment. Considerable upregulation of genes related to autophagy and apoptosis suggests that autophagy boosts cisplatin efficacy in malignant ACHN cells with minimal harm to normal HEK-293 growth. Furthermore, the determination of cellular viability and apoptosis by AnnexinV/FITC-PI assay corroborates with in silico data, indicating the reliability of the bioinformatics method followed by qRT-PCR. Altogether, our data provide a clear molecular insight into drug efficacy under starved conditions to improve chemotherapy and will likely prompt more clinical trials on this aspect.
摘要：
顺铂,一种强大的化疗药物，由于化疗失败，长期以来一直是抗击癌症的基石。顺铂耐药/失败的机制是一个多方面的复杂问题，主要包括通过自噬敏化抑制细胞凋亡。目前,研究人员正在探索调节自噬的方法，以调整平衡，有利于有效的化疗。基于这个概念,本研究主要通过IlluminaHi-seq平台鉴定顺铂处理的自噬ACHN细胞中的差异表达基因(DEGs).使用STRING数据库和KEGG构建了蛋白质-蛋白质相互作用网络。涉及GO分类器以鉴定基因及其参与的生物学途径。Cluego,大卫,和MCODE检测到本体丰富和子网。使用12种不同的算法进一步检查网络拓扑，以通过Cytoscape插件Cytohubba识别排名最高的集线器基因，以识别潜在的目标，在自噬环境下建立了深刻的药物功效。与自噬和凋亡相关的基因的大量上调表明自噬增强了恶性ACHN细胞中顺铂的功效，对正常HEK-293生长的伤害最小。此外，通过AnnexinV/FITC-PI测定法测定细胞活力和细胞凋亡与计算机数据证实，表明生物信息学方法和qRT-PCR方法的可靠性。总之,我们的数据为在饥饿条件下改善化疗的药物疗效提供了清晰的分子见解，并可能促使在这方面进行更多的临床试验。
