PMID: 15248904Jul 14, 2004Paper

Indomethacin induces apoptosis through inhibition of survivin regulated by beta-catenin/TCF4 in human colorectal cancer cells

Ai zheng = Aizheng = Chinese journal of cancer
Hongxia ZhuNingzhi Xu

Abstract

Although Wnt pathway plays important role in colorectal carcinogenesis, but the mechanism of this pathway in anti-apoptosis is not clear. This study is to investigate the molecular mechanism of Wnt pathway in anti-apoptosis. Survivin promoter region was constructed into luciferase reporter system (pGL3-sur1.8kb). The recombinants pGL3-sur1.8kb were cotransfected with pRL-SV40 into HCT116 cells and the activities were detected with Dual-luciferase reporter assay system. Cell apoptosis was analyzed by flow cytometry. Protein level of survivin and beta-catenin was detected by Western Blot. Survivin could be up-regulated by beta-catenin and down-regulated by TCF4DeltaN in transcriptional level. beta-catenin/TCF4 dependent apoptosis induced by indomethacin could suppress survivin transcription. Overexpression of survivin could partially recover the beta-catenin/TCF4 dependent apoptosis. Down-regulation of survivin affected by beta-catenin/TCF4 pathway plays an important role in apoptosis induced by NSAIDs indomethacin in HCT116 cells. The beta-catenin/TCF4-survivin pathway may be a potential target in treatment of colon cancer.

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