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丹参酮 IIA 通过诱导铁死亡抑制胃癌干细胞特性。

Tanshinone IIA inhibits gastric cancer cell stemness through inducing ferroptosis.

机构信息

School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.

Department of Pharmacy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Environ Toxicol. 2022 Feb;37(2):192-200. doi: 10.1002/tox.23388. Epub 2021 Oct 18.

Abstract

Tanshinone IIA is the active constituent extracted from Salvia Miltiorrhza. Numerous studies have shown that Tanshinone IIA could inhibit tumor proliferation and metastasis, including gastric cancer. However, the effect of Tanshinone IIA on gastric cancer cell stemness stays unclear. Here, we found that Tanshinone IIA could reduce gastric cancer cell stemness through detecting spheroid-forming, flow cytometry analysis, and the expression of stemness markers (OCT3/4, ALDH1A1, and CD44). Mechanistically, Tanshinone IIA increased the level of lipid peroxides and decreased glutathione level in gastric cancer cells, both of which are the markers of ferroptosis. Similarly, ferroptosis inducers (erastin, sulfasalazine, and sorafenib) reduced gastric cancer cell stemness. Additionally, the inhibitory effects of Tanshinone IIA on GC cell stemness were reversed by ferroptosis inhibitor (Fer-1) or overexpression of SLC7A11, which is a critical ferroptosis inhibitor. Therefore, we revealed that Tanshinone IIA inhibited the stemness of gastric cancer cells partly through inducing ferroptosis.

摘要

丹参酮 IIA 是从丹参中提取的有效成分。大量研究表明,丹参酮 IIA 可以抑制肿瘤的增殖和转移,包括胃癌。然而,丹参酮 IIA 对胃癌细胞干性的影响尚不清楚。在这里,我们发现丹参酮 IIA 可以通过检测球体形成、流式细胞术分析和干性标志物(OCT3/4、ALDH1A1 和 CD44)的表达来降低胃癌细胞干性。在机制上,丹参酮 IIA 增加了胃癌细胞中的脂质过氧化物水平并降低了谷胱甘肽水平,这两者都是铁死亡的标志物。同样,铁死亡诱导剂(erastin、柳氮磺胺吡啶和索拉非尼)降低了胃癌细胞干性。此外,铁死亡抑制剂(Fer-1)或 SLC7A11 的过表达逆转了丹参酮 IIA 对 GC 细胞干性的抑制作用,SLC7A11 是一种关键的铁死亡抑制剂。因此,我们揭示了丹参酮 IIA 通过诱导铁死亡部分抑制胃癌细胞的干性。

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