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学科主题临床医学
The COX-2 selective inhibitor-independent COX-2 effect on colon carcinoma cells is associated with the Delta1/Notch1 pathway
Zhang, Hui; Ye, Yingjiang; Bai, Zhigang; Wang, Shan
关键词apoptosis colon carcinoma cyclooxygenase-2 inhibitor Notch signal transduction proliferation
刊名DIGESTIVE DISEASES AND SCIENCES
2008-08-01
DOI10.1007/s10620-007-0139-0
53期:8页:2195-2203
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
研究领域[WOS]Gastroenterology & Hepatology
关键词[WOS]GAMMA-SECRETASE INHIBITOR ; CANCER-CELLS ; INDUCED APOPTOSIS ; SIGNALING PATHWAY ; NOTCH ; CYCLOOXYGENASE-2 ; DIFFERENTIATION ; ACTIVATION ; INDUCTION ; CELECOXIB
英文摘要

Background Cyclooxygenase-2 (COX-2) is a key factor in the development of colorectal cancer, and non-steroidal anti-inflammatory drugs (NSAIDs) have anti-colorectal cancer activity. However, the potential molecular mechanism of the COX-2 selective inhibitor effect on proliferation and apoptosis of colon cancer cells is unclear. In this study, we have demonstrated for the first time that the Delta1/Notch1 signal transduction pathway mediates the COX-2 selective inhibitor effect on colorectal cancer cells, and we reveal the mechanism of the Notch1 pathway in terms of regulating the proliferation and apoptosis of colorectal cancer cells. Methods and Result Colon cancer cell lines HT-29 and SW480 were treated with NS-398 (a COX-2 selective inhibitor) and DAPT (a gamma-secretase inhibitor). The colormetric MTT cell proliferation assay and flow cytometry were used to measure cell proliferation and apoptosis. Reverse transcriptase (RT)-PCR and ELISA analyses were used to detect the levels of COX-2 mRNA expression and prostaglandin E2 (PGE2) concentration from the two cell lines, respectively. The expression of the Notch1, Delta1, ICN, Hes1 and NF-kappa B2 proteins was measured by Western blot. Immunohistochemistry results showed that Notch1 was expressed mainly in the cytoplasm and ICN mainly in the nucleus. COX-2 mRNA was highly expressed in HT-29 cells but not in SW480 cells. Both COX-2 mRNA expression and PGE2 concentration decreased in HT-29 cells treated with NS-398; however, PGE2 levels did not change in SW480 cells treated with NS-398. NS-398 and DAPT inhibited cell proliferation and induced apoptosis in a dose time-dependent manner accompanied by significantly decreased Notch1 activity (P < 0.01), and resulted in a significant down-regulation of Hes1 and NF-kappa B2 (P < 0.01). Conclusions Our results show that the selective COX-2 inhibitor may inhibit the proliferation and induce apoptosis in colon cancer cells through the COX-2-dependent pathway (HT-29) by decreasing the COX-2 mRNA/PGE2 levels and the activity of the COX-2-independent pathway (SW480). The Notch1 signal pathway mediates the effects of the COX-2 inhibitor on the proliferation and apoptosis of colon cancer cells. This may be a new target of the selective COX-2 inhibitor effect on colon cancer.

语种英语
WOS记录号WOS:000257328000027
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62350
专题北京大学第二临床医学院_肿瘤科
作者单位1.Peking Univ, Peoples Hosp, Surg Oncol Lab, Beijing 100044, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Surg Gastroenterol, Beijing 100044, Peoples R China
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GB/T 7714
Zhang, Hui,Ye, Yingjiang,Bai, Zhigang,et al. The COX-2 selective inhibitor-independent COX-2 effect on colon carcinoma cells is associated with the Delta1/Notch1 pathway[J]. DIGESTIVE DISEASES AND SCIENCES,2008,53(8):2195-2203.
APA Zhang, Hui,Ye, Yingjiang,Bai, Zhigang,&Wang, Shan.(2008).The COX-2 selective inhibitor-independent COX-2 effect on colon carcinoma cells is associated with the Delta1/Notch1 pathway.DIGESTIVE DISEASES AND SCIENCES,53(8),2195-2203.
MLA Zhang, Hui,et al."The COX-2 selective inhibitor-independent COX-2 effect on colon carcinoma cells is associated with the Delta1/Notch1 pathway".DIGESTIVE DISEASES AND SCIENCES 53.8(2008):2195-2203.
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