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PTPN9的表达下调通过抑制STAT3活化促进结直肠癌细胞凋亡

PTPN9 induces Apoptosis of Colorectal cancer Cell via Mitigating the Activation of STAT3

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【作者】 朱兴业赵明汪大伟屈春雷王伟

【Author】 ZHU Xing-ye;ZHAO Ming;WANG Da-wei;QU Chun-lei;WANG wei;Department of General Surgery, the First Affiliated Hospital of Harbin Medical University;

【通讯作者】 赵明;

【机构】 哈尔滨医科大学附属第一医院肛肠外科

【摘要】 目的:探讨PTPN9对结直肠癌细胞生长和存活的影响及其机制。方法:建立稳定PTPN9高表达的细胞系,使用Real-timePCR检测其内源性变达,使用细胞集落实验及Caspase-3、Caspase-9,检测其细胞活力及凋亡情况。同时我们抑制了细胞中PTPN9的表达,使用实时PCR来验证敲低效率,应用100μM H2O2诱导凋亡模型,利用CCK-8测定来确定细胞活力,Caspase-9和Cas-pase-3测定检测其凋亡情况。最后我们应用Western blot技术,检测PTPN9抑制STAT3通路,来调控细胞凋亡。结果:PTPN9的表达在结直肠癌组织中下调。PTPN9的高表达减慢细胞生长和集落的形成,从而诱导结直肠癌细胞凋亡。相反,PTPN9低表达促进细胞生长和存活。此外,PTPN9负责调控STAT3的活化,并在结直肠癌中抑制核易位,并且通过抑制STAT3通路,来抑制PTPN9低表达对细胞凋亡的影响。结论:PTPN9在结直肠癌组织中通过抑制STAT3的活化而抑制细胞生长和存活。

【Abstract】 Objective: To investigate the effect of Protein tyrosine phosphatase non-receptor type 9(PTPN9) on the growth and survival of colorectal cancer cells and its mechanism. Methods: A stable cell line with high expression of PTPN9 was established, the endogenous expression of PTPN9 was detected by Real-time PCR. Cell colony assay, Caspase-3 and Caspase-9 activity were used to detect cell viability and apoptosis. At the same time, we inhibited the expression of PTPN9 in the cells. Real-time PCR was used to verify knockdown efficiency. 100 μM H2O2-induced apoptosis model, CCK-8 assay was used to determine cell viability, Caspase-9 and Caspase-3 assay to detect the apoptosis. Finally, we applied Western blot technology to detect PTPN9 inhibition of STAT3 pathway to regulate apoptosis. Results: The expression of PTPN9 was frequently down-regulated in the tissues of colorectal cancer as compared with their adjacent normal tissues. Overexpression of PTPN9 mitigated cell growth and colony formation and induced cell apoptosis in colorectal cancer. Conversely, PTPN9 knockdown promoted cell growth and survival. Moreover, PTPN9 negatively regulated the activation of STAT3 and depressed its nuclear translocation in colorectal cancer. And the effects of PTPN9 knockdown on cell apoptosis were attenuated by inhibition of the STAT3 pathway. Conclusions: PTPN<sub> inhibited the growth and survival of colorectal cancer cells via repressing the activation of STAT3.

【基金】 中国国家博士后科学基金项目(2012M520769);国家自然科学基金青年基金项目(81600492)
  • 【文献出处】 现代生物医学进展 ,Progress in Modern Biomedicine , 编辑部邮箱 ,2019年02期
  • 【分类号】R735.34
  • 【被引频次】1
  • 【下载频次】74
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