Abstract：
Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated.
Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3).
Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting.
Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect.
All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.
Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3).
Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting.
Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect.
All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.
摘要：
背景：脂质代谢参与各种生物过程，例如增殖，凋亡，迁移,入侵,和维持前列腺肿瘤细胞的膜稳态。Bufadienolides,禅素的活性成分，在体外对前列腺癌细胞显示出强大的抗增殖作用，但是bufadienolides是否可以调节前列腺癌的脂质代谢尚未被评估。
目的：我们的研究探讨了bufadienolides对人前列腺癌细胞（PC-3）脂质代谢的调节作用。
方法：结合非靶向脂质组学和转录组学研究不同的bufadienolides干预对PC-3细胞脂质和基因变化的影响。通过qPCR和western印迹验证了与脂质代谢和前列腺癌发展相关的关键基因。
结果：脂质组学分析显示，活性bufadienolides显著下调PC-3细胞长链脂质的含量。基于转录组和qPCR分析，许多与脂质代谢相关的基因被活性的bufadienolides显著调节，例如ELOVL6、CYP2E1、GAL3ST1、CERS1、PLA2G10、PLD1、SPTLC3和GPX2。对癌症基因组图谱数据库的生物信息学分析和文献检索表明，极长链脂肪酸蛋白6（ELOVL6）和磷脂酶D1（PLD1）的延伸可能是重要的调控基因。Westernblot分析显示，活性bufadienolides可以下调PLD1蛋白水平，这可能会促进抗前列腺癌作用。
结论：所有这些发现支持bufadenolides可能通过调节长链脂质合成和磷脂水解来诱导脂质代谢重塑，从而达到抗前列腺癌的作用。PLD1可能是关键蛋白质。
目的：我们的研究探讨了bufadienolides对人前列腺癌细胞（PC-3）脂质代谢的调节作用。
方法：结合非靶向脂质组学和转录组学研究不同的bufadienolides干预对PC-3细胞脂质和基因变化的影响。通过qPCR和western印迹验证了与脂质代谢和前列腺癌发展相关的关键基因。
结果：脂质组学分析显示，活性bufadienolides显著下调PC-3细胞长链脂质的含量。基于转录组和qPCR分析，许多与脂质代谢相关的基因被活性的bufadienolides显著调节，例如ELOVL6、CYP2E1、GAL3ST1、CERS1、PLA2G10、PLD1、SPTLC3和GPX2。对癌症基因组图谱数据库的生物信息学分析和文献检索表明，极长链脂肪酸蛋白6（ELOVL6）和磷脂酶D1（PLD1）的延伸可能是重要的调控基因。Westernblot分析显示，活性bufadienolides可以下调PLD1蛋白水平，这可能会促进抗前列腺癌作用。
结论：所有这些发现支持bufadenolides可能通过调节长链脂质合成和磷脂水解来诱导脂质代谢重塑，从而达到抗前列腺癌的作用。PLD1可能是关键蛋白质。
