期刊
INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
卷 36, 期 7, 页码 632-639出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.ijom.2007.04.003
关键词
signal transducer and activator of transcription 3 (Stat3); survivin; COX; head and neck cancer; squamous cell carcinoma; sulindac
资金
- NIDCR NIH HHS [DE13118, DE12606] Funding Source: Medline
Sulindac exerts its antitumourigenic effects in oral squamous cell carcinoma (SCC) cells by modulating survivin in a Stat3-dependent manner. Immunohistochemistry was used to detect the protein levels of phosphorylated-tyrosine Stat3 (p-tyr Stat3) and survivin in SCC tissues. Western blot, reverse transcriptase polymerase chain reaction, Annexin-V and cell proliferation assays were used to determine p-tyr Stat3 and survivin protein and mRNA expression, and cell viability following treatment with cyclooxygenase (COX) inhibitors, Stat3 siRNA, or the forced expression of Stat3 or survivin. Immunohistochemical analysis revealed an overexpression of p-tyr Stat3 in T1 SCCs. The importance of constitutive Stat3 activation in tumourigenesis was confirmed by siRNA inhibition of Stat3, resulting in cell growth inhibition and apoptosis, via a downregulation of survivin mRNA and protein expression. The forced expression of survivin partially reversed these effects of Stat3 inhibition. Sulindac, but not other COX inhibitors, downregulated Stat3, which correlated to an inhibition of cell proliferation, survival and survivin expression. Transfection of constitutively active Stat3 resorted survivin expression and partially rescued SCC cells from sulindac-induced antitumourigenic effects. These data indicate that survivin is a downstream target and effector of oncogenic Stat3 signalling in SCC, which is targeted by sulindac in a COX-2-independent manner.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据