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SHCBP1通过磷酸酶和张力蛋白同源物调节肺癌细胞中的细胞凋亡。

SHCBP1 regulates apoptosis in lung cancer cells through phosphatase and tensin homolog.

作者信息

Wang Fei, Li Yi, Zhang Zhe, Wang Jingxin, Wang Jinghao

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

Department of Neurology, Harbin Children's Hospital, Harbin, Heilongjiang 150086, P.R. China.

出版信息

Oncol Lett. 2019 Aug;18(2):1888-1894. doi: 10.3892/ol.2019.10520. Epub 2019 Jun 24.

DOI:10.3892/ol.2019.10520
PMID:31423258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6614682/
Abstract

Src homologous and collagen (SHC) SH2-binding protein 1 (SHCBP1) is a member of the SHC family, and is overexpressed in numerous types of cancer. In addition, apoptosis serves an important role in the development of cancer. The purpose of this study was to examine the effect of SHCBP1 on apoptosis and its potential underlying mechanism in lung cancer cells. Apoptosis was detected by flow cytometry and caspase-3 activity analysis. The expression levels of SHCBP1 and phosphatase and tensin homolog (PTEN) were detected by western blot analysis and reverse transcription-quantitative polymerase chain reaction. Cell viability was determined by MTT assay. The results indicated that SHCBP1 was increased in lung cancer cell lines and lung cancer tissues compared with in normal lung cell lines and tissues. The apoptosis of lung cancer cells was significantly increased by SHCBP1 small interfering RNA (siRNA), as indicated by the increased number of apoptotic cells and enhanced caspase-3 activity. In addition, it was demonstrated that PTEN expression was modulated by SHCBP1 knockdown; silencing of SHCBP1 expression led to a significant increase in PTEN expression. Furthermore, inhibition of PTEN by siRNA reversed the increase in apoptosis induced by SHCBP1 siRNA. These results suggested that SHCBP1 may be upregulated in lung cancer and it may serve a key role in the apoptosis of lung cancer cells; this effect was associated with the expression of PTEN.

摘要

Src同源和胶原蛋白(SHC)SH2结合蛋白1(SHCBP1)是SHC家族的成员,在多种类型的癌症中过表达。此外,细胞凋亡在癌症发展中起重要作用。本研究的目的是检测SHCBP1对肺癌细胞凋亡的影响及其潜在的作用机制。通过流式细胞术和半胱天冬酶-3活性分析检测细胞凋亡。通过蛋白质印迹分析和逆转录-定量聚合酶链反应检测SHCBP1和磷酸酶及张力蛋白同源物(PTEN)的表达水平。通过MTT法测定细胞活力。结果表明,与正常肺细胞系和组织相比,肺癌细胞系和肺癌组织中SHCBP1升高。SHCBP1小干扰RNA(siRNA)显著增加了肺癌细胞的凋亡,表现为凋亡细胞数量增加和半胱天冬酶-3活性增强。此外,证明PTEN表达受SHCBP1敲低调节;SHCBP1表达沉默导致PTEN表达显著增加。此外,siRNA抑制PTEN可逆转SHCBP1 siRNA诱导的凋亡增加。这些结果表明,SHCBP1可能在肺癌中上调,并且可能在肺癌细胞凋亡中起关键作用;这种作用与PTEN的表达有关。

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Inhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/ Pathway in Lung Adenocarcinoma A549 Cells.通过下调肺腺癌A549细胞中的PI3K/AKT/信号通路抑制细胞增殖、促进细胞凋亡并诱导细胞周期停滞。
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SHCBP1 is over-expressed in breast cancer and is important in the proliferation and apoptosis of the human malignant breast cancer cell line.
SHCBP1 抑制剂 AZD5582 在胰腺癌治疗中的治疗潜力。
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