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皂苷在前列腺癌中的抗肿瘤活性及潜在生物标志物

Anti-tumor activities of saponins and potential biomarkers in prostate cancer.

作者信息

He Shan, Lyu Fangqiao, Lou Lixia, Liu Lu, Li Songlin, Jakowitsch Johannes, Ma Yan

机构信息

Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology & Immunology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.

Department of Cell Biology, School of Basic Medicine, Capital Medical University, Beijing, China.

出版信息

J Ginseng Res. 2021 Mar;45(2):273-286. doi: 10.1016/j.jgr.2019.12.007. Epub 2020 Jan 7.

DOI:10.1016/j.jgr.2019.12.007
PMID:33841008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8020356/
Abstract

BACKGROUND

Prostate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC.

METHODS

We used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes.

RESULTS

Our data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2.

CONCLUSION

PQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.

摘要

背景

前列腺癌是全球男性中第二常见的癌症。开发前列腺癌(PC)的新治疗方法和诊断生物标志物具有重大需求。据报道,中药皂苷(PQS)具有抗肿瘤作用。我们假设PQS在人PC细胞中具有抗癌活性,并且旨在寻找能够早期诊断PC的新型生物标志物。

方法

我们使用人PC细胞系DU145和前列腺上皮细胞系PNT2进行细胞活力测定、细胞周期的流式细胞术分析以及基于FACS的凋亡测定。基于微阵列的基因表达分析用于显示特定的基因表达模式并寻找新型生物标志物。进行蛋白质免疫印迹和定量实时PCR以证明多个癌症相关基因的表达水平。

结果

我们的数据表明,PQS抑制DU145细胞的活力并诱导细胞周期停滞在G1期。PQS处理24小时后,观察到DU145细胞的侵袭和迁移显著减少。PQS上调p21、p53、TMEM79、ACOX1、ETV5和SPINT1的表达水平,同时下调bcl2、STAT3、FANCD2、DRD2和TMPRSS2的表达水平。

结论

PQS促进细胞凋亡并抑制DU145细胞的增殖,这表明PQS可能对治疗PC有效。TMEM79和ACOX1在PNT2中的表达明显高于DU145细胞,可能是PC诊断的新型生物标志物候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/b7bd8bde0f17/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/8eed9833e7e5/gr1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/c6187eb69f4b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/453fc01b106e/gr4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/b7bd8bde0f17/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/8eed9833e7e5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/262916536d45/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/c6187eb69f4b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/453fc01b106e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/83ddb7f96afe/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/27bd924f8f6b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/1fe65bd8cdac/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/ad8e766750c5/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/23bb14e9abb3/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c5/8020356/b7bd8bde0f17/gr10.jpg

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