Chen Shushang, Weng Mingfang, Lin Ronghui, Wei Junjie, Zhu Lingfeng, Ju Zhenghua, Lin Zhitao, Zhan Bin, Pathak Ram A, Sayyid Rashid K, Ge Rong
Department of Urology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Department of Urology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China.
Transl Androl Urol. 2024 Oct 31;13(10):2294-2306. doi: 10.21037/tau-24-457. Epub 2024 Oct 28.
New medications are needed to improve outcomes of castration-resistant prostate cancer (CRPC). Psoralen has been reported to have anti-cancer properties for various tumors, but there are limited reports about psoralen treatment in prostate cancer (PCa). This study aimed to investigate the effect of psoralen on PC3 cells and to investigate potential underlying mechanisms of action.
The effect of psoralen on the proliferation and cell cycle progression of PC3 cells was determined using Cell Counting Kit-8 (CCK-8) test and flow cytometry, respectively. The differential gene profiles in PC3 cells treated with psoralen were determined with microarray analyses. The effect of psoralen on long non-coding RNA (lncRNA) ENST00000510619 expression in PC3 cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of psoralen and transfection of small interfering lnc-RNA (si-lncRNA) ENST00000510619 on cell viability, invasion ability, and migratory activity of PC3 cells were evaluated using the CCK-8 test, transwell assay, and wound healing, respectively.
Psoralen significantly inhibited PC3 cells in a concentration- and time-dependent manner and caused G1 phase and G2/M phase cycle arrests. When screened with a fold change (FC) of ≥2 and a P value of <0.05, 1,716 lncRNAs and 1,160 messenger RNAs (mRNAs) were significantly up-regulated, whereas 3,269 lncRNAs and 3,263 mRNAs were significantly down-regulated in PC3 cells after psoralen treatment. Among the differentially down-regulated lncRNAs in which the signal of the probe showed significant differences compared to the background, lncRNA ENST00000510619 had the highest FC. The expression of lncRNA ENST00000510619 was shown to be down-regulated by psoralen in a concentration-dependent manner. CCK-8 assay, wound healing, and transwell assay showed that both psoralen and si-lncRNA ENST00000510619 transfection significantly inhibited the activity, invasion, and migration of PC3 cells (P<0.01 for all).
Psoralen was confirmed to inhibit proliferation and block the cell cycle in PC3 cells in this study. The molecular mechanism involves multiple differentially expressed lncRNAs and mRNAs and is related to the down-regulation of lncRNA ENST000000510619 expression. This study provides the experimental basis for the development of psoralen as a novel anti-CRPC drug and for the consideration of lncRNA ENST00000510619 as a potential clinical target for CRPC.
需要新的药物来改善去势抵抗性前列腺癌（CRPC）的治疗效果。补骨脂素已被报道对多种肿瘤具有抗癌特性，但关于补骨脂素治疗前列腺癌（PCa）的报道有限。本研究旨在探讨补骨脂素对PC3细胞的作用及其潜在的作用机制。
分别使用细胞计数试剂盒-8（CCK-8）试验和流式细胞术测定补骨脂素对PC3细胞增殖和细胞周期进程的影响。通过微阵列分析确定补骨脂素处理的PC3细胞中的差异基因谱。通过实时定量聚合酶链反应（RT-qPCR）检测补骨脂素对PC3细胞中长链非编码RNA（lncRNA）ENST00000510619表达的影响。分别使用CCK-8试验、Transwell试验和伤口愈合试验评估补骨脂素和小干扰lncRNA（si-lncRNA）ENST00000510619转染对PC3细胞活力、侵袭能力和迁移活性的影响。
补骨脂素以浓度和时间依赖性方式显著抑制PC3细胞，并导致G1期和G2/M期细胞周期停滞。当以≥2的倍数变化（FC）和<0.05的P值进行筛选时，补骨脂素处理后的PC3细胞中，1716个lncRNA和1160个信使RNA（mRNA）显著上调，而3269个lncRNA和3263个mRNA显著下调。在与背景相比探针信号显示出显著差异的差异下调lncRNA中，lncRNA ENST00000510619的FC最高。补骨脂素以浓度依赖性方式下调lncRNA ENST00XXX051XX9的表达。CCK-8试验、伤口愈合试验和Transwell试验表明，补骨脂素和si-lncRNA ENST00000510619转染均显著抑制PC3细胞的活性、侵袭和迁移（所有P<0.01）。
本研究证实补骨脂素可抑制PC3细胞的增殖并阻断其细胞周期。分子机制涉及多个差异表达的lncRNA和mRNA，且与lncRNA ENST000000510619表达下调有关。本研究为补骨脂素作为一种新型抗CRPC药物的开发以及将lncRNA ENST00000510619视为CRPC的潜在临床靶点提供了实验依据。
