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小檗碱通过调节角蛋白 17 抑制宫颈癌细胞活力和转移。

Berberine modulates Keratin 17 to inhibit cervical cancer cell viability and metastasis.

机构信息

Department of Obstetrics and Gynecology, Yantai Hospital of Traditional Chinese Medicine, Yantai, China.

出版信息

J Recept Signal Transduct Res. 2021 Dec;41(6):521-531. doi: 10.1080/10799893.2020.1830110. Epub 2020 Oct 12.

DOI:10.1080/10799893.2020.1830110
PMID:33045871
Abstract

AIM

Berberine (BBR) acts as a tumor suppressor in different cancer cells. Our paper exerted efforts to discover the effect of BBR on cervical cancer.

METHODS

Human cervical cancer cell lines SiHa and Ca Ski were treated with different concentrations of BBR. Cell viability, apoptosis, migration and invasion were detected by MTT assay, flow cytometry, wound healing assay, and Transwell assay, respectively. Expressions of Bcl-2-associated X protein (Bax), Bcl-2, cleaved (C) caspase-3 and epithelial-mesenchymal transition (EMT)-related proteins were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Keratin 17 (KRT17) expression in cervical cancer was identified by GEPIA2 and qRT-PCR. Rescue assay was then performed to assess the functional interaction between BBR and KRT17.

RESULTS

Human cervical cancer cell viability, migration, and invasion were inhibited by BBR. BBR promoted cell apoptosis by increasing Bax and C caspase-3 expressions and decreasing Bcl-2 expression. Besides, BBR inhibited EMT in cells by decreasing the expressions of MMP-9, N-cadherin and Vimentin and increasing E-cadherin expression. Effects of BBR on cervical cancer cells were in a dose-dependent manner. Higher expression of KRT17 was found in cervical cancer SiHa and Ca Ski cells. BBR rescued the effects of KRT17 on promoting cell viability, metastasis, and the expressions of Bcl-2, MMP-9, N-cadherin and Vimentin, and suppressing apoptosis and the expressions of Bax, C-caspase-3 and E-cadherin.

CONCLUSION

BBR inhibited cervical cancer cell viability, metastasis and EMT but promoted cell apoptosis suppressing KRT 17 expression.

摘要

目的

小檗碱(BBR)在不同的癌细胞中作为肿瘤抑制因子发挥作用。我们的论文致力于发现 BBR 对宫颈癌的影响。

方法

用不同浓度的 BBR 处理人宫颈癌细胞系 SiHa 和 Ca Ski。通过 MTT 测定、流式细胞术、划痕愈合试验和 Transwell 试验分别检测细胞活力、凋亡、迁移和侵袭。通过实时定量聚合酶链反应(qRT-PCR)和 Western blot 测定 Bcl-2 相关 X 蛋白(Bax)、Bcl-2、裂解(C)半胱天冬酶-3 和上皮-间充质转化(EMT)相关蛋白的表达。通过 GEPIA2 和 qRT-PCR 鉴定宫颈癌中角蛋白 17(KRT17)的表达。然后进行挽救实验以评估 BBR 和 KRT17 之间的功能相互作用。

结果

BBR 抑制人宫颈癌细胞活力、迁移和侵袭。BBR 通过增加 Bax 和 C 半胱天冬酶-3 的表达和降低 Bcl-2 的表达来促进细胞凋亡。此外,BBR 通过降低 MMP-9、N-钙黏蛋白和波形蛋白的表达以及增加 E-钙黏蛋白的表达抑制细胞中的 EMT。BBR 对宫颈癌细胞的作用呈剂量依赖性。在宫颈癌 SiHa 和 Ca Ski 细胞中发现 KRT17 表达较高。BBR 挽救了 KRT17 对促进细胞活力、转移以及 Bcl-2、MMP-9、N-钙黏蛋白和波形蛋白表达、抑制细胞凋亡以及 Bax、C 半胱天冬酶-3 和 E-钙黏蛋白表达的影响。

结论

BBR 抑制宫颈癌细胞活力、转移和 EMT,但通过抑制 KRT17 表达促进细胞凋亡。

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