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α-山竹黄酮通过阻断Stat3信号通路在体外抑制人胃腺癌细胞。

α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway.

作者信息

Shan Tao, Cui Xi-juan, Li Wei, Lin Wan-run, Lu Hong-wei, Li Yi-ming, Chen Xi, Wu Tao

机构信息

Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, China.

Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.

出版信息

Acta Pharmacol Sin. 2014 Aug;35(8):1065-73. doi: 10.1038/aps.2014.43. Epub 2014 Jun 30.

Abstract

AIM

To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects.

METHODS

Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot.

RESULTS

Treatment with α-mangostin (3-10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells.

CONCLUSION

The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway.

摘要

目的

研究山竹果(莽吉柿,学名:Garcinia mangostana Linn)果皮中主要的氧杂蒽酮类化合物α-倒捻子素对人胃腺癌细胞的体外抗肿瘤作用及其作用机制。

方法

用α-倒捻子素处理人胃腺癌细胞系BGC-823和SGC-7901。采用MTT法检测细胞活力,用流式细胞术和TUNEL法检测细胞凋亡。用蛋白质免疫印迹法检测相关蛋白的表达。

结果

α-倒捻子素(3 - 10μg/mL)处理以剂量和时间依赖的方式抑制BGC-823和SGC-7901细胞的活力。此外,α-倒捻子素(7μg/mL)能时间依赖性地增加癌细胞的凋亡指数,降低癌细胞的线粒体膜电位,并显著增加细胞色素c和凋亡诱导因子向细胞质中的释放。而且,α-倒捻子素处理明显抑制癌细胞中组成型Stat3蛋白的激活以及Stat3调节的Bcl-xL和Mcl-1蛋白水平。

结论

α-倒捻子素对人胃腺癌细胞的体外抗肿瘤作用部分归因于对Stat3信号通路的阻断。

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