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用于检测半乳糖凝集素-3抑制剂对前列腺癌治疗效果的拉曼光谱方法。

Raman spectroscopic modality to examine therapeutic efficacy of Galectin-3 inhibitor in prostate cancer.

作者信息

Ghazanfarpour Samaneh, Sheikhsofla Alireza, Pourrahimi Monireh, Sharma Satish, Skomra Andrew, Sharikova Anna, Schwartz Stanley A, Mahajan Supriya D, Khmaladze Alexander, Aalinkeel Ravikumar

机构信息

Department of Physics, University at Albany SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA.

Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Clinical Translational Research Center, Buffalo, NY, 14203, USA; Department of Urology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

出版信息

Biochem Biophys Res Commun. 2025 Apr 9;757:151646. doi: 10.1016/j.bbrc.2025.151646. Epub 2025 Mar 15.

Abstract

Glycoproteins, such as Galectin-3 (Gal-3) and Prostate Specific Membrane Antigen (PSMA), are functional proteins involved in numerous biological activities that include cell apoptosis, angiogenesis, and inflammation. Downregulation of both in the highly metastatic human Prostate Cancer (CaP) cell line PC-3 reduces tumor growth. We used Raman Spectroscopy (RS) to examine the effect of a potent Gal-3 inhibitor (GB1107) in CaP cell lines of varying metastatic potential, namely PC-3, DU-145 and LNCaP. All three cancer lines had distinct Raman signatures. Raman spectra from PC-3, DU-145 and LNCaP cells treated with GB1107, compared to the untreated cells as controls, showed significant differences corresponding to changes in phosphatidylinositol (peak at 596 cm), O-P-O stretching DNA (786 cm), lipid/phospholipid DNA backbone (1090-1100 cm), nucleic acid, lipid, protein (amide III) (1296-1305 cm), fatty acid (1440 cm), and protein (amid I) (1655 cm), suggesting that DNA phosphate backbone may become unstable with cancer progression, facilitating cancer cell metastasis. Our data suggests that Gal-3 inhibitor induces significant alterations in major biochemical constituents, such as lipids, proteins, and nucleic acids, which may lead to structural and molecular changes in the cancerous prostate tissue. To further analyze these spectral differences, Singular Value Decomposition (SVD) and Linear Discriminant Analysis (LDA) were applied for classification, enabling effective differentiation between treated and untreated CaP cell lines. This highlights the therapeutic potential of Gal-3 inhibitor in prevention of CaP progression and metastases.

摘要

糖蛋白,如半乳糖凝集素-3(Gal-3)和前列腺特异性膜抗原(PSMA),是参与众多生物活动的功能蛋白,这些活动包括细胞凋亡、血管生成和炎症。在高转移性人前列腺癌细胞系PC-3中下调这两种蛋白均可减少肿瘤生长。我们使用拉曼光谱(RS)来研究一种有效的Gal-3抑制剂(GB1107)对不同转移潜能的前列腺癌细胞系(即PC-3、DU-145和LNCaP)的影响。所有这三种癌细胞系都有独特的拉曼特征峰。与作为对照的未处理细胞相比,用GB1107处理的PC-3、DU-145和LNCaP细胞的拉曼光谱显示出与磷脂酰肌醇(596 cm处的峰)、O-P-O拉伸DNA(786 cm)、脂质/磷脂DNA主链(1090 - 1100 cm)、核酸、脂质、蛋白质(酰胺III)(1296 - 1305 cm)、脂肪酸(1440 cm)和蛋白质(酰胺I)(1655 cm)变化相对应的显著差异,这表明DNA磷酸主链可能随着癌症进展而变得不稳定,从而促进癌细胞转移。我们的数据表明,Gal-3抑制剂可诱导脂质、蛋白质和核酸等主要生化成分发生显著变化,这可能导致癌性前列腺组织发生结构和分子变化。为了进一步分析这些光谱差异,应用奇异值分解(SVD)和线性判别分析(LDA)进行分类,从而能够有效区分处理过的和未处理的前列腺癌细胞系。这突出了Gal-3抑制剂在预防前列腺癌进展和转移方面的治疗潜力。

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