用一种合成肽靶向雄激素受体（AR）可增加三阴性乳腺癌和表达AR的前列腺癌细胞系中的细胞凋亡。

Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR-expressing prostate cancer cell lines.

作者信息

Jamshidi Mazdak, Keshavarzi Fatemeh, Amini Sabrieh, Laher Ismail, Gheysarzadeh Ali, Davari Kambiz

机构信息

Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.

Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

Cancer Rep (Hoboken). 2024 Jan;7(1):e1922. doi: 10.1002/cnr2.1922. Epub 2023 Oct 30.

DOI:10.1002/cnr2.1922

PMID:37903548

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10809188/

Abstract

BACKGROUND

The androgen receptor (AR) has been studied as an approach to cancer therapy.

AIMS

We used human breast cancer-derived cells with high, low, and very low expression levels of AR, in addition to prostate cancer-derived LNCaP and DU-145 cells as a positive and negative controls to examine apoptosis caused by a synthetic peptide that targets ARs.

METHODS AND RESULTS

The peptide was produced to inhibit AR transactivation in breast cancer cell lines. We then measured cell viability, caspase-3 activity, and the ratio of Bax/Bcl-2. The findings indicated that the peptide (100-500 nM) in the presence of dihydrotestosterone (DHT) reduced cell growth in cells with high and low expression level of AR (p < .001), but not in cells with very low levels of AR. Treatment with 100-500 nM of peptide activated caspase-3 and increased the ratio of Bax/Bcl-2 in cells with high and low expression levels of AR. Also, increasing concentrations of the peptide (100-500 nM) reduced BrdU incorporation in the presence of DHT and promoted apoptosis in cells with high and low expression levels of AR (p < .001).

CONCLUSION

The findings indicate the peptide significantly increased apoptosis in cancer cells.

摘要

背景

雄激素受体（AR）已作为一种癌症治疗方法进行研究。

目的

我们使用了人乳腺癌来源的细胞，其AR表达水平分别为高、低和极低，此外还使用了前列腺癌来源的LNCaP和DU - 145细胞作为阳性和阴性对照，以检测一种靶向AR的合成肽所引起的细胞凋亡。

方法与结果

该肽被制备用于抑制乳腺癌细胞系中的AR反式激活。然后我们测量了细胞活力、半胱天冬酶 - 3活性以及Bax/Bcl - 2的比率。结果表明，在存在二氢睾酮（DHT）的情况下，该肽（100 - 500 nM）可降低AR高表达和低表达细胞中的细胞生长（p < 0.001），但对AR极低表达的细胞无此作用。用100 - 500 nM的肽处理可激活AR高表达和低表达细胞中的半胱天冬酶 - 3并增加Bax/Bcl - 2的比率。此外，在存在DHT的情况下，增加肽的浓度（100 - 500 nM）可减少BrdU掺入，并促进AR高表达和低表达细胞中的细胞凋亡（p < 0.001）。