Integrative Bioinformatics and Experimental Validation Reveal theMechanistic Action of Patchouli Alcohol in Prostate Cancer Treatment

前列腺癌 下调和上调 广藿香 DU145型 癌症研究 前列腺 癌症 医学 生物 基因 内科学 生物化学 病理 替代医学 LNCaP公司
作者
Songhui Zhai,Juan Zhao,Jian Cai
出处
期刊:Current Pharmaceutical Biotechnology [Bentham Science Publishers]
卷期号:27
标识
DOI:10.2174/0113892010355513241224101450
摘要

Introduction: Prostate cancer is an androgen-dependent malignancy, and the use of androgen deprivation therapies frequently results in treatment resistance, relapse, and the development of aggressive castration-resistant tumors. Patchouli alcohol, a tricyclic sesquiterpene derived from Pogostemon cablin of the Labiatae family, has demonstrated potential in modulating inflammatory responses and tumor progression. This study aimed to investigate the mechanisms through which patchouli alcohol influences inflammatory pathways associated with prostate cancer using bioinformatics and experimental validation. Methods: Differentially Expressed Genes (DEGs) were identified from the GSE46602 dataset, containing 36 prostate cancer and 14 normal prostate biopsy samples, using the GEO2R tool (adjusted P < 0.05). Functional annotation was performed using GO and KEGG databases, while PPI networks were constructed via STRING and Cytoscape. Key hub genes were identified. To validate the bioinformatics findings, qPCR and Western blotting were employed to confirm the differential expression of selected hub genes in DU145 prostate cancer cells treated with patchouli oil. Results: Bioinformatic analysis revealed 71 DEGs, including 35 upregulated and 36 downregulated genes. Thirteen hub genes were identified (DCK, APRT, ADK, KCNK9, ADSL, PKM, KCNK3, S100A10, ENTPD2, PKLR, ARHGEF38, TPK1, and AK5), which were enriched in pathways, such as MAPK, PI3K-Akt, Ras, and Rap1. Experimental validation confirmed the upregulation of DCK, APRT, KCNK9, ADSL, PKM, S100A10, ENTPD2, PKLR, ARHGEF38, and AK5, and the downregulation of ADK, KCNK3, and TPK1 at both the mRNA and protein levels. Conclusion: Patchouli alcohol appears to influence multiple hub genes associated with prostate cancer progression through its modulation of key cellular signaling and metabolic pathways. These findings support its potential role as a therapeutic agent for prostate cancer.
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