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光黄素通过抑制自噬增强电离辐射对卵巢癌干细胞样细胞的作用。

Lumiflavin Enhances the Effects of Ionising Radiation on Ovarian Cancer Stem-Like Cells by Inhibiting Autophagy.

机构信息

Department of Pharmacology, Vocational and Technical College, Lishui University, Lishui, 323000, China.

Department of Anatomy and Histoembryology, College of Medicine and Health, Lishui University, Lishui, 323000, China.

出版信息

Anticancer Agents Med Chem. 2021;21(15):2004-2011. doi: 10.2174/1871520621999210104201907.

DOI:10.2174/1871520621999210104201907
PMID:33397270
Abstract

BACKGROUND

The development of Cancer Stem-like Cells (CSCs) is one of the main causes of ovarian cancer tolerance to radiotherapy. Autophagy is an adaptive process by which cells damage due to radiation. As a metabolite of riboflavin, lumiflavin can enhance the chemotherapeutic effects of cisplatin on ovarian cancer CSCs.

OBJECTIVE

This study aimed to investigate the synergistic effects of lumiflavin and ionising radiation on ovarian cancer CSCs and explore the association of this metabolite with autophagy.

METHODS

CSCs of human ovarian cancer cell lines HO8910 were treated with lumiflavin and rapamycin and then subjected to irradiation at a cumulative dose of 8 Gy. Cell proliferation ability, clonal formation ability, apoptosis rate, autophagy changes and autophagy-related protein changes were detected.

RESULTS

Lumiflavin and ionising radiation synergistically reduced cell vitality and clone formation and increased the apoptosis of CSCs compared with irradiation alone. In addition, ionising radiation increased autophagy and the expression of associated proteins, whereas lumiflavin reduced those changes in autophagy progression. Moreover, rapamycin, an autophagy inhibitor, was observed to block the synergistic effects of lumiflavin and ionising radiation on CSC apoptosis.

CONCLUSION

Lumiflavin can enhance the effects of ionising radiation on ovarian cancer CSCs. The mechanism by which these effects are exerted is related to blocking the autophagy pathway.

摘要

背景

癌症干细胞样细胞(CSC)的发展是卵巢癌对放疗耐受的主要原因之一。自噬是一种细胞适应性过程,可导致细胞因辐射而受损。黄素单核苷酸作为核黄素的代谢产物,可增强顺铂对卵巢癌 CSC 的化疗作用。

目的

本研究旨在探讨黄素单核苷酸与电离辐射对卵巢癌 CSC 的协同作用,并探讨该代谢物与自噬的关系。

方法

用黄素单核苷酸和雷帕霉素处理人卵巢癌细胞系 HO8910 的 CSC,然后接受 8 Gy 的累积剂量照射。检测细胞增殖能力、克隆形成能力、细胞凋亡率、自噬变化和自噬相关蛋白变化。

结果

与单纯照射相比,黄素单核苷酸和电离辐射协同降低了 CSC 的活力和克隆形成能力,并增加了细胞凋亡。此外,电离辐射增加了自噬和相关蛋白的表达,而黄素单核苷酸降低了自噬进展的这些变化。此外,自噬抑制剂雷帕霉素观察到可阻断黄素单核苷酸和电离辐射对 CSC 凋亡的协同作用。

结论

黄素单核苷酸可增强电离辐射对卵巢癌 CSC 的作用。这些作用的发挥机制与阻断自噬途径有关。

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核黄素通过诱导分化降低OVCAR-3细胞系癌干细胞样细胞中的顺铂耐药性。
Front Oncol. 2022 May 20;12:859275. doi: 10.3389/fonc.2022.859275. eCollection 2022.