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解析相互作用:噻吩并[2,3-]吡啶对卵巢肿瘤细胞系中糖脂表达、细胞毒性、细胞凋亡和代谢组学的影响。

Deciphering the Interplay: Thieno[2,3-]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines.

机构信息

Department of Gynecology and Obstetrics, University Hospital of Split, 21000 Split, Croatia.

Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia.

出版信息

Int J Mol Sci. 2024 Jun 25;25(13):6954. doi: 10.3390/ijms25136954.

Abstract

Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino--(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-]quinoline-2-carboxamide (Compound ), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f, and non-CSCs (CD49f) were explored. Treatment with Compound reduced the percentage of CSCs compared to non-treated cells ( < 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound resulted in statistically meaningful increased apoptosis, including both early and late apoptosis ( < 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group ( < 0.001).

摘要

卵巢癌是女性死亡的主要原因之一。尽管诊断方法有所改进,但非特异性症状和延迟的妇科检查可能导致晚期卵巢肿瘤的发现。在这项研究中,研究了一种抗癌化合物 3-氨基-(3-氯-2-甲基苯基)-5-氧代-5,6,7,8-四氢噻吩并[2,3-d]喹啉-2-甲酰胺(化合物)的作用。研究了细胞毒性、凋亡和卵巢癌细胞系 SK-OV-3 和 OVCAR-3 中的代谢变化,以及糖脂(GSL)表达对癌症干细胞(CSC),标记为 CD49f,和非 CSC(CD49f)的影响。与未处理的细胞相比,用化合物处理后 CSC 的百分比降低(<0.001)。使用流式细胞术检查了八种 GSL 对 CSC 和非 CSC 的功能影响。在两种细胞系中,在用化合物处理后,其表达增加或减少,导致糖表型发生变化。这些发现为卵巢癌治疗中特异性靶向 CSC 提供了可能性。此外,用化合物处理导致统计学上有意义的凋亡增加,包括早期和晚期凋亡(<0.001),这表明在通过凋亡途径启动程序性细胞死亡方面发挥了关键作用。分析表明,与对照组相比,处理后的癌细胞的代谢活性较低(<0.001)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b620/11241605/798843ec6755/ijms-25-06954-g001.jpg

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