虽然许多研究支持内分泌干扰物（EDs）与肿瘤的进展和恶性程度之间存在剂量效应关系，但长期暴露于非致死浓度的ED对癌症的影响仍未知。更具体地说，许多研究报道了Aldrin对多种癌症类型（包括前列腺癌）的影响。在以前的研究中，我们证明长期暴露于Aldrin（一种ED）后可以诱导DU145前列腺癌（PCa）细胞的恶性表型。蛋白质在调控和控制各种细胞过程中至关重要。然而，ED对PCa影响的机制以及蛋白质在此过程中的作用尚不明确。本文采用两种互补的计算方法来研究前列腺癌恶性过程的分子机制。首先，通过约束代谢建模，将转录组和代谢组学相结合，研究了长期暴露于Aldrin的DU145细胞中与代谢重编程相关的过程。其次，应用基因集富集分析来确定（i）变化的调节通路和（ii）Aldrin暴露细胞转录组剖面的变化与各种癌症的肿瘤进展之间的相关性。实验证实预测，显示出代谢和调节通路的失调。这种改变导致了蛋白质水平的改变，这些蛋白质对调节三酰甘油/胆固醇至关重要，与Aldrin暴露细胞观察到的恶性表型相关。

Although numerous studies support a dose-effect relationship between Endocrine disruptors (EDs) and the progression and malignancy of tumors, the impact of a chronic exposure to non-lethal concentrations of EDs in cancer remains unknown. More specifically, a number of studies have reported the impact of Aldrin on a variety of cancer types, including prostate cancer. In previous studies, we demonstrated the induction of the malignant phenotype in DU145 prostate cancer (PCa) cells after a chronic exposure to Aldrin (an ED). Proteins are pivotal in the regulation and control of a variety of cellular processes. However, the mechanisms responsible for the impact of ED on PCa and the role of proteins in this process are not yet well understood. Here, two complementary computational approaches have been employed to investigate the molecular processes underlying the acquisition of malignancy in prostate cancer. First, the metabolic reprogramming associated with the chronic exposure to Aldrin in DU145 cells was studied by integrating transcriptomics and metabolomics via constraint-based metabolic modeling. Second, gene set enrichment analysis was applied to determine (i) altered regulatory pathways and (ii) the correlation between changes in the transcriptomic profile of Aldrin-exposed cells and tumor progression in various types of cancer. Experimental validation confirmed predictions revealing a disruption in metabolic and regulatory pathways. This alteration results in the modification of protein levels crucial in regulating triacylglyceride/cholesterol, linked to the malignant phenotype observed in Aldrin-exposed cells.