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宫颈癌中PIAS3, SHP2和SOCS3的表达模式:STAT3信号的活化和白藜芦醇引起的灭活的关系

PIAS3, SHP2 and SOCS3 Expression patterns in Cervical Cancers: Relevance with activation and resveratrol-caused inactivation of STAT3 signaling

来源:Scopus 发布时间:2016-1-6
作者:Zhang, P., Yang, B., Yao, Y.-Y., Zhong, L.-X., Chen, X.-Y., Kong, Q.-Y., Wu, M.-L., Li, C., Li, H. , Liu, J.
机构: 大连医科大学基础医学院 细胞生物学系 辽宁省肿瘤遗传和表观遗传学实验室
期刊: GYNECOL ONCOL2015年12月3期139卷

Objective Resveratrol inhibits cervical cancer (CC) cells by blocking STAT3 signaling. However, the mechanism of resveratrol-induced STAT3 inactivation remains largely unknown. SHP2, PIAS3, and SOCS3 are STAT3 negative regulators; therefore, their statuses in cervical adenocarcinoma (HeLa) and squamous cell carcinoma (SiHa and C33A) cell lines without and with resveratrol treatment and their correlation with STAT3 activation in CC specimens were investigated. Methods MTT and TUNEL assays were used to check the resveratrol sensitivity of CC cells, and immunocytochemical staining, Western blotting, and RT-PCR were used to analyze SHP2, PIAS3, and SOCS3 expression and the intracellular distribution of STAT3. Tissue microarray based immunohistochemical staining was performed to investigate potential correlations between SHP2, PIAS3, and SOCS3 expression and STAT3 activation. Results PIAS3 and SOCS3 were found to be weakly expressed in CC cells and upregulated by resveratrol; this was accompanied by inhibition of STAT3 signaling. The SHP2 level remained unchanged in all three cell lines after resveratrol treatment. STAT3 nuclear translocation was more frequent in adenocarcinomas and squamous cell carcinomas than that of their noncancerous counterparts. The SOCS3 level and detection rate were higher in noncancerous squamous cells (but not in glandular epithelia) compared with their cancerous counterparts. The phospho-SHP2 detection rate was similar in noncancerous and tumor tissues of squamous and glandular origins; however, PIAS3 levels were distinct. Conclusions Of the three STAT3 negative regulators, PIAS3 correlated most negatively with STAT3 nuclear translocation and may inhibit STAT3 signaling in both histological CC subtypes. PIAS3 responsiveness may reflect greater resveratrol sensitivity and improved therapeutic outcome in CCs. © 2015 Elsevier Inc. All rights reserved.

 

通讯作者:Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Lvshun South Road, Dalian, China
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