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小檗碱通过抑制 p38/JNK 通路、诱导线粒体介导的细胞凋亡、半胱天冬酶激活和 NF-κB 抑制来抑制人胃癌细胞生长。

Berberine inhibits human gastric cancer cell growth via deactivation of p38/JNK pathway, induction of mitochondrial-mediated apoptosis, caspase activation and NF-κB inhibition.

机构信息

Department of General Surgery, Xinyang Central Hospital, Henan, China.

出版信息

J BUON. 2020 Jan-Feb;25(1):314-318.

PMID:32277648
Abstract

PURPOSE

Gastric cancer accounts for considerable mortality across the globe. In this study the anticancer effects of a natural compound Berberine were investigated in vitro. Effects of berberine on cell migration, cellular apoptosis, Nf-kB and JNK/p38 signalling pathways were also studied.

METHODS

The cell viability of SNU-1 gastric cancer cells after berberine treatment was evaluated by CCK-8 assay, while the effects on cell migration were checked by wound healing assay. Effects on cellular apoptosis were evaluated by fluorescence microscopy using DAPI staining, as well as using flow cytometry with annexin V/propidium iodide (PI) staining. Effects on apoptosis-related protein expressions were checked by western blot method.

RESULTS

The results showed that Berberine decreased the viability of the gastric cancer SNU-1 cells and exhibited an IC50 of 30 µM. The cytoxicity of Berberine was also investigated on the normal GES-1 gastric cells and it was found that Berberine exerted very low toxic effects on these cells and exhibited an IC50 of 120 µM. Berberine also caused remarkable changes in the morphology of the SNU-1 cells. PI and DAPI staining revealed that Berberine prompted apoptosis of the SNU-1 cells in a dose-dependent manner. The apoptotic cells increased from 2.2% in control to around 35% at 30 µM concentration. Berberine also suppressed the migration and invasion of the gastric cancer cells via blocking of the JNK/p38 signalling pathway.

CONCLUSIONS

Berberine may act as a promising drug candidate for gastric cancer as demonstrated from the current study.

摘要

目的

胃癌在全球范围内导致了相当高的死亡率。在这项研究中,研究了天然化合物小檗碱对体外胃癌的抗癌作用。还研究了小檗碱对细胞迁移、细胞凋亡、Nf-kB 和 JNK/p38 信号通路的影响。

方法

通过 CCK-8 测定法评估 SNU-1 胃癌细胞在小檗碱处理后的细胞活力,通过划痕愈合测定法检查对细胞迁移的影响。通过 DAPI 染色的荧光显微镜以及用 Annexin V/PI(PI)染色的流式细胞术评估细胞凋亡的影响。通过 Western blot 法检查凋亡相关蛋白表达的影响。

结果

结果表明,小檗碱降低了胃癌 SNU-1 细胞的活力,并表现出 30µM 的 IC50。还研究了小檗碱对正常 GES-1 胃细胞的细胞毒性,发现小檗碱对这些细胞的毒性作用非常低,IC50 为 120µM。小檗碱还使 SNU-1 细胞的形态发生了明显变化。PI 和 DAPI 染色表明,小檗碱以剂量依赖的方式促使 SNU-1 细胞凋亡。凋亡细胞从对照中的 2.2%增加到 30µM 浓度时约 35%。小檗碱还通过阻断 JNK/p38 信号通路抑制胃癌细胞的迁移和侵袭。

结论

从目前的研究来看,小檗碱可能是一种有前途的胃癌候选药物。

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