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β-榄香烯通过 IGF1/IGF1R 通路诱导三阴性乳腺癌细胞凋亡和衰老。

β-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1/IGF1R pathway.

机构信息

Department of Oncology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine; Liangzhu hospital, Yuhang district, Hangzhou, China.

Department of Oncology, Liangzhu hospital, Yuhang district, Hangzhou, China.

出版信息

Tissue Cell. 2022 Dec;79:101914. doi: 10.1016/j.tice.2022.101914. Epub 2022 Sep 1.

DOI:10.1016/j.tice.2022.101914
PMID:36183441
Abstract

PURPOSE

β-elemene has a wide range of anticancer effects and can be used in a variety of cancer types. This study mainly explored its mechanism of action on TNBC cells and provided theoretical basis for the treatment of TNBC.

METHODS

Firstly, TNBC cells were treated with different concentrations of β-elemene, and screened out an appropriate concentration for subsequent research. Then, through the bioinformatics website, predicted genes that have a binding relationship with β-elemene. Then, the overexpression vector of the selected gene was transfected into the cell. The effects of β-elemene and its target genes on the proliferation and apoptosis of TNBC cells were detected by CCK-8, Edu assay, and flow cytometry, and the senescence of cells was determined by SA-β-gal experiment. Western blotting was used to detect the expression of apoptosis and aging-related proteins.

RESULTS

β-elemene inhibited TNBC cell viability and proliferation in a concentration-dependent manner, and induces apoptosis and senescence. Through the screening of candidate genes, IGF1 was finally determined to be an effective target gene of β-elemene. The expression level of IGF1 was decreased in cells treated with β-elemene. Overexpression of IGF1 significantly alleviated ability of β-elemene to inhibit cell viability, proliferation, and induced cell apoptosis and senescence. In addition, β-elemene inhibited the expression of IGF1R and Bcl-2, and promoted the expression of Cleaved Caspase-3 and senescence-related proteins (p27, p16, p53 and p21), and these effects were reversed by overexpression of IGF1.

CONCLUSION

β-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1/IGF1R pathway.

摘要

目的

β-榄香烯具有广泛的抗癌作用,可用于多种癌症类型。本研究主要探讨其对三阴性乳腺癌(TNBC)细胞的作用机制,为 TNBC 的治疗提供理论依据。

方法

首先用不同浓度的β-榄香烯处理 TNBC 细胞,筛选出适合后续研究的浓度。然后,通过生物信息学网站预测与β-榄香烯具有结合关系的基因。接着,将选定基因的过表达载体转染入细胞。通过 CCK-8、Edu 检测和流式细胞术检测β-榄香烯及其靶基因对 TNBC 细胞增殖和凋亡的影响,通过 SA-β-gal 实验检测细胞衰老。Western blot 检测凋亡和衰老相关蛋白的表达。

结果

β-榄香烯呈浓度依赖性抑制 TNBC 细胞活力和增殖,并诱导细胞凋亡和衰老。通过候选基因的筛选,最终确定 IGF1 是β-榄香烯的有效靶基因。β-榄香烯处理的细胞中 IGF1 的表达水平降低。过表达 IGF1 可显著减轻β-榄香烯抑制细胞活力、增殖的能力,并诱导细胞凋亡和衰老。此外,β-榄香烯抑制 IGF1R 和 Bcl-2 的表达,促进 Cleaved Caspase-3 和衰老相关蛋白(p27、p16、p53 和 p21)的表达,而过表达 IGF1 则逆转了这些作用。

结论

β-榄香烯通过 IGF1/IGF1R 通路诱导三阴性乳腺癌细胞凋亡和衰老。

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