Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

被引：34

作者：

Li, Xiaofeng ^{[1
]}

Zhang, Xiaoting ^{[1
]}

Liu, Xizhi ^{[1
]}

Tan, Zhiwen ^{[1
]}

Yang, Celi ^{[1
]}

Ding, Xiaofeng ^{[1
,2
]}

Hu, Xiang ^{[1
,2
]}

Zhou, Jianlin ^{[1
]}

Xiang, Shuanglin ^{[1
,2
]}

Zhou, Chang ^{[1
,2
]}

Zhang, Han ^{[1
]}

机构：

[1] Hunan Normal Univ, Coll Life Sci, Key Lab Prot Chem & Dev Biol, State Educ Minist China, Changsha 410081, Hunan, Peoples R China

[2] Hunan Inst Biol, Changsha 410006, Hunan, Peoples R China

来源：

ONCOLOGY REPORTS | 2013年 / 30卷 / 02期

基金：

中国国家自然科学基金;

关键词：

caudatin; beta-catenin; cell apoptosis; gastric cancer cells; miRNA; CLINICAL-SIGNIFICANCE; LINE SMMC7721; PATHWAY; EXPRESSION; MICRORNAS; MECHANISM; CARCINOMA; KINASE;

D O I：

10.3892/or.2013.2495

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Caudatin has been reported to trigger apoptosis in several types of cancer cell lines. In the present study, we investigated whether caudatin has therapeutic value in gastric cancer and examined the effects of caudatin on the expression of beta-catenin in human gastric carcinoma cell lines. Here, we showed that caudatin treatment resulted in a dose- and time-dependent inhibition of proliferation of the gastric carcinoma cell lines. Cell cycle analysis demonstrated that caudatin induced G0/G1 arrest and downregulated CDK2 levels. In contrast, the expression of the p21 protein was increased. AGS cells treated with caudatin exhibited typical characteristics of apoptosis, which were accompanied by activation of caspase-3, -8,-9 and PARP. Western blot analysis and immunocytochemical staining showed that caudatin induced a reduction in beta-catenin expression and this reduction was due to proteosome-mediated degradation. This reduction in beta-catenin activation was due to the downregulation of its downstream targets cyclinD1 and c-MYC in all gastric carcinoma cell lines. Furthermore, we demonstrated that gastric adenocarcinoma tissues and AGS cells exhibited abnormal expression of miR-372. Additionally, caudatin downregulated the expression of oncomir miR-372 and miR-21, and upregulated tumor suppressor let-7a miRNA expression. These data revealed that inhibition of Wnt/beta-catenin signaling is a novel mechanism of action for caudatin during therapeutic intervention in gastric cancers.

引用

页码：677 / 684

页数：8

共 38 条

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