Licochalcone A Inhibits Proliferation and Metastasis of Colon Cancer by Regulating miR-1270/ADAM9/Akt/NF-κB axis

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-09-09 DOI:10.18502/ijph.v52i9.13578

Changhai Pan, Hongjin Chen, Bolin Yang

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引用次数: 0

Abstract

Background: We aimed to explor the therapeutic effect and molecular mechanism of licochalcone A (LCA) on colon cancer. Methods: This study was carried out in 2020-2021 in Nanjing Tongren Hospital, China. Colon cancer HCT116 cells were treated with different concentrations of LCA. Cell counting kit-8, colony formation and flow cytometry assays were used to analyze cell viability, proliferation and apoptosis. Wound healing and transwell experiments were used to measure cell migration and invasion ability. The expression of ADAM9 and apoptosis-related proteins in different LCA treatment groups was detected by western blot. HCT116 cells were transfected with ADAM9 small interfering RNAs (siRNAs) or overexpression vectors. The database screened the upstream miRNA targeting ADAM9 and predicted the targeted binding site between miR-1270 and ADAM9, which was verified by a dual-luciferase reporter assay. Rescue experiments were performed to confirm the effects of the miR-1270/ADAM9 axis on cell proliferation and metastasis. Results: LCA decreased cell growth (P<0.05), migration (P<0.05), and invasion (P<0.05) of colon cancer cells and inhibited ADAM9 expression in a dose-dependent manner. LCA affected the functions of colon cancer cells by negatively regulating the expression of ADAM9. MiR-1270, increased by LCA, targeted and suppressed ADAM9 expression significantly (P<0.001). ADAM9 overexpression restrained miR-1270 mimic and LCA-induced changes in cell proliferation, migration, and invasion, and promoted apoptosis in HCT116 cells significantly (P<0.01). LCA and miR-1270 mimic inactivated the Akt/NF-κB pathway, while ADAM9 overexpression rescued it. Conclusion: LCA exhibited antitumor efficacy in HCT116 cells by inhibiting the Akt/NF-κB signaling pathway by regulating the miR-1270/ADAM9 axis.

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甘草查尔酮A通过调控miR-1270/ADAM9/Akt/NF-κB轴抑制结肠癌增殖和转移

背景:探讨甘草查尔酮A (licochalcone A, LCA)治疗结肠癌的疗效及分子机制。方法:本研究于2020-2021年在中国南京同仁医院进行。用不同浓度的LCA处理结肠癌HCT116细胞。细胞计数试剂盒-8、集落形成和流式细胞术检测细胞活力、增殖和凋亡。创面愈合和transwell实验检测细胞迁移和侵袭能力。western blot检测不同LCA处理组ADAM9及凋亡相关蛋白的表达。用ADAM9小干扰rna (sirna)或过表达载体转染HCT116细胞。数据库筛选上游靶向ADAM9的miRNA，预测miR-1270与ADAM9的靶向结合位点，并通过双荧光素酶报告基因实验进行验证。通过挽救实验证实miR-1270/ADAM9轴对细胞增殖和转移的影响。结果:LCA降低结肠癌细胞的生长(P<0.05)、迁移(P<0.05)和侵袭(P<0.05)，抑制ADAM9的表达，并呈剂量依赖性。LCA通过负向调节ADAM9的表达影响结肠癌细胞的功能。LCA增加的MiR-1270靶向并显著抑制ADAM9的表达(P<0.001)。ADAM9过表达抑制miR-1270模拟和lca诱导的细胞增殖、迁移和侵袭的变化，并显著促进HCT116细胞的凋亡(P<0.01)。LCA和miR-1270模拟Akt/NF-κB通路失活，而ADAM9过表达使其恢复。结论:LCA通过调节miR-1270/ADAM9轴抑制Akt/NF-κB信号通路，对HCT116细胞具有抗肿瘤作用。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.