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姜黄素通过调节C-Myc和PI3K/Akt信号通路诱导EJ膀胱癌细胞凋亡。

Curcumin Induces Apoptosis in EJ Bladder Cancer Cells via Modulating C-Myc and PI3K/Akt Signaling Pathway.

作者信息

Wang Jingyu, Wang Zhiping, Wang Hanzhang, Zhao Junli, Zhang Zhewen

机构信息

Institute of Pathophysiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.

Institute of Urology, Second Hospital, Lanzhou University, Lanzhou, 730030, China.

出版信息

World J Oncol. 2011 Jun;2(3):113-122. doi: 10.4021/wjon335w. Epub 2011 Jun 8.

Abstract

BACKGROUND

Cancer chemopreventive agent curcumin has been shown to possess cell growth inhibition and apoptosis induction properties in several types of cancer. However, the detailed molecular mechanisms of the compound remain far from clear in EJ bladder cancer cells.

METHODS

The effect of curcumin on EJ cell growth and apoptosis was detected by MTT assays and flow cytometry. The phosphorylation levels of PTEN, PDK1, Akt, GSK-3β, c-Raf, and Bad and the expression levels of c-myc, Bax, Bcl-2, caspase-9, caspase-7, caspase-3, and PARP following curcumin administration were examined by immunoblots.

RESULTS

Curcumin suppressed the growth of EJ cells in a time and concentration dependent manner. Immunoblot showed that curcumin increased expression levels of c-myc and inhibited the activation of PI3K/Akt pathway in a time-dependent manner in EJ cells. Activation of PTEN, GSK-3β, c-Raf, caspase-9, caspase-7, and caspase-3, cleavage of PARP, upregulation of Bad and Bax, and downregulation of Akt and Bcl-2 were also found in curcumin-treated EJ cells.

CONCLUSIONS

These findings establish a mechanistic linkup or interaction between c-myc, Bax, Bad, Bcl-2, caspase cascades, PI3K/Akt pathway and curcumin- induced apoptosis of EJ cells, suggesting that c-myc and PI3K/Akt signaling pathway play important roles in curcumin-induced apoptosis of EJ bladder cancer cells.

摘要

背景

癌症化学预防剂姜黄素已被证明在多种类型的癌症中具有细胞生长抑制和诱导凋亡的特性。然而,在EJ膀胱癌细胞中,该化合物的详细分子机制仍远未明确。

方法

通过MTT法和流式细胞术检测姜黄素对EJ细胞生长和凋亡的影响。通过免疫印迹法检测给予姜黄素后PTEN、PDK1、Akt、GSK-3β、c-Raf和Bad的磷酸化水平以及c-myc、Bax、Bcl-2、caspase-9、caspase-7、caspase-3和PARP的表达水平。

结果

姜黄素以时间和浓度依赖性方式抑制EJ细胞的生长。免疫印迹显示,姜黄素在EJ细胞中以时间依赖性方式增加c-myc的表达水平并抑制PI3K/Akt途径的激活。在姜黄素处理的EJ细胞中还发现了PTEN、GSK-3β、c-Raf、caspase-9、caspase-7和caspase-3的激活、PARP的切割、Bad和Bax的上调以及Akt和Bcl-2的下调。

结论

这些发现建立了c-myc、Bax、Bad、Bcl-2、caspase级联反应、PI3K/Akt途径与姜黄素诱导的EJ细胞凋亡之间的机制联系或相互作用,表明c-myc和PI3K/Akt信号通路在姜黄素诱导的EJ膀胱癌细胞凋亡中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f63/5649664/63ad8dd79dbe/wjon-02-113-g001.jpg

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