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在人源肿瘤异种移植(PDTX)模型中,PLK1通过MEK-ERK途径作为胃癌潜在的预后标志物。

PLK1 as a potential prognostic marker of gastric cancer through MEK-ERK pathway on PDTX models.

作者信息

Dang Sheng-Chun, Fan Yi-Yi, Cui Lei, Chen Ji-Xiang, Qu Jian-Guo, Gu Min

机构信息

Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.

Zhenjiang Integrative Medicine Hospital, Zhenjiang, Jiangsu Province, People's Republic of China,

出版信息

Onco Targets Ther. 2018 Sep 25;11:6239-6247. doi: 10.2147/OTT.S169880. eCollection 2018.

DOI:10.2147/OTT.S169880
PMID:30288059
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6163028/
Abstract

BACKGROUND

PLK1 has been identified as having a great effect on cell division and maintaining genomic stability in mitosis, spindle assembly, and DNA damage response by current studies.

MATERIALS AND METHODS

We assessed PLK1 expression in cervical cancer tissues and cells. We have also evaluated the effects of PLK1 on gastric cancer cell proliferation, migration, and apoptosis both in vitro and in vivo.

RESULTS

Our results show that PLK1 is overexpressed in gastric cancer tissues and cells. Inhibition of PLK1 contributes cell cycle G2-phase arrest and inhibits the proliferation, migration, and apoptosis of gastric cancer (GC) cells, whereas its overexpression promotes proliferation, migration, and apoptosis in these cells. Moreover, PLK1 inhibition reduces expression of pMEK and pERK. More importantly, in vivo by analyzing tumorigenesis in patient-derived tumor xenograft (PDTX) models, the inhibition of PLK1 activity by BI6727 significantly decreased the volume and weight of the tumors compared with control group (<0.01).

CONCLUSION

Our results found that PLK1 has a significant impact on the survival of GC cells; it may become a prognostic judge, a potential therapeutic target, and a preventative biomarker of GC.

摘要

背景

目前的研究已证实,PLK1在细胞分裂以及维持有丝分裂过程中的基因组稳定性、纺锤体组装和DNA损伤反应方面具有重要作用。

材料与方法

我们评估了PLK1在宫颈癌组织和细胞中的表达情况。我们还在体外和体内评估了PLK1对胃癌细胞增殖、迁移和凋亡的影响。

结果

我们的研究结果表明,PLK1在胃癌组织和细胞中过表达。抑制PLK1会导致细胞周期G2期阻滞,并抑制胃癌(GC)细胞的增殖、迁移和凋亡,而其过表达则会促进这些细胞的增殖、迁移和凋亡。此外,抑制PLK1会降低pMEK和pERK的表达。更重要的是,在体内通过分析患者来源的肿瘤异种移植(PDTX)模型中的肿瘤发生情况,与对照组相比,BI6727抑制PLK1活性显著降低了肿瘤的体积和重量(<0.01)。

结论

我们的研究结果发现,PLK1对GC细胞的存活有显著影响;它可能成为GC的预后判断指标、潜在治疗靶点和预防生物标志物。

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