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热休克蛋白27(HSP27)、细胞凋亡抑制蛋白(cFLIP)和簇集蛋白(CLU)基因的三重沉默增强了多沙唑嗪诱导PC-3前列腺癌细胞凋亡的敏感性。

Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells.

作者信息

Cho Jeong Man, Sun Sojung, Im Eunji, Yang Hyunwon, Yoo Tag Keun

机构信息

Department of Urology, Uijeongbu Eulji Medical Center, Uijeongbu 11759, Republic of Korea.

Department of Biohealth Convergence, Seoul Women's University, Seoul 01797, Republic of Korea.

出版信息

Medicines (Basel). 2024 Feb 21;11(3):7. doi: 10.3390/medicines11030007.

Abstract

This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.

摘要

本研究调查了热休克蛋白27(HSP27)、细胞FLICE样抑制蛋白(cFLIP)和簇集素(CLU)的表达如何影响癌细胞的进展及其对多沙唑嗪诱导凋亡的敏感性。通过单独沉默这些基因中的每一个,研究了它们对多沙唑嗪处理后前列腺癌细胞活力的影响。培养PC-3前列腺癌细胞,然后使用靶向HSP27、cFLIP和CLU的小干扰RNA(siRNA)单独、成对或一起进行基因沉默。然后用不同浓度的多沙唑嗪处理细胞,并通过MTT法评估其活力。研究发现,在PC-3细胞中沉默CLU基因显著降低了用25µM多沙唑嗪处理后的细胞活力。此外,cFLIP和CLU的双重沉默在10µM多沙唑嗪时降低了细胞活力。值得注意的是,沉默HSP27、cFLIP、CLU这三个基因最为有效,甚至在1µM的较低多沙唑嗪浓度下也降低了细胞活力。综上所述,这些发现表明,同时沉默HSP27、cFLIP和CLU基因可能是促进前列腺癌细胞凋亡的一种潜在策略,这可为未来恶性前列腺癌治疗的研究提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eeaf/10971947/991a57758532/medicines-11-00007-g001.jpg

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