Department of Ultrasound, Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital), Shaoxing, Zhejiang, China.
Department of Gynaecology and Obstetrics, Xinchang County People's Hospital, Xinchang, Zhejiang, China.
Technol Health Care. 2024;32(6):3889-3902. doi: 10.3233/THC-231051.
Matrine has been reported inhibitory effects on ovarian cancer (OC) cell progression, development, and apoptosis. However, the molecular targets of matrine against OC and the underlying mechanisms of action remain elusive.
This study endeavors to unveil the potential targets of matrine against OC and to explore the intricate relationships between these targets and the pathogenesis of OC.
The effects of matrine on the OC cells (A2780 and AKOV3) viability, apoptosis, migration, and invasion was investigated through CCK-8, flow cytometry, wound healing, and Transwell analyses, respectively. Next, Matrine-related targets, OC-related genes, and ribonucleic acid (RNA) sequence data were harnessed from publicly available databases. Differentially expressed analyses, protein-protein interaction (PPI) network, and Venn diagram were involved to unravel the core targets of matrine against OC. Leveraging the GEPIA database, we further validated the expression levels of these core targets between OC cases and controls. Mendelian randomization (MR) study was implemented to delve into potential causal associations between core targets and OC. The AutoDock software was used for molecular docking, and its results were further validated using RT-qPCR in OC cell lines.
Matrine reduced the cell viability, migration, invasion and increased the cell apoptosis of A2780 and AKOV3 cells (P< 0.01). A PPI network with 578 interactions among 105 candidate targets was developed. Finally, six core targets (TP53, CCND1, STAT3, LI1B, VEGFA, and CCL2) were derived, among which five core targets (TP53, CCND1, LI1B, VEGFA, and CCL2) differential expressed in OC and control samples were further picked for MR analysis. The results revealed that CCND1 and TP53 were risk factors for OC. Molecular docking analysis demonstrated that matrine had good potential to bind to TP53, CCND1, and IL1B. Moreover, matrine reduced the expression of CCND1 and IL1B while elevating P53 expression in OC cell lines.
We identified six matrine-related targets against OC, offering novel insights into the molecular mechanisms underlying the therapeutic effects of matrine against OC. These findings provide valuable guidance for developing more efficient and targeted therapeutic approaches for treating OC.
苦参碱已被报道对卵巢癌（OC）细胞的进展、发展和凋亡具有抑制作用。然而，苦参碱针对 OC 的分子靶点以及作用机制仍不清楚。
本研究旨在揭示苦参碱针对 OC 的潜在靶点，并探讨这些靶点与 OC 发病机制之间的复杂关系。
通过 CCK-8、流式细胞术、划痕愈合和 Transwell 分析分别研究苦参碱对 OC 细胞（A2780 和 AKOV3）活力、凋亡、迁移和侵袭的影响。接下来，从公共数据库中获取苦参碱相关靶点、OC 相关基因和核糖核酸（RNA）序列数据。进行差异表达分析、蛋白质-蛋白质相互作用（PPI）网络和 Venn 图分析，以揭示苦参碱针对 OC 的核心靶点。利用 GEPIA 数据库进一步验证 OC 病例和对照之间这些核心靶点的表达水平。实施孟德尔随机化（MR）研究以深入探讨核心靶点与 OC 之间的潜在因果关系。使用 AutoDock 软件进行分子对接，并在 OC 细胞系中使用 RT-qPCR 进一步验证其结果。
苦参碱降低了 A2780 和 AKOV3 细胞的细胞活力、迁移、侵袭，增加了细胞凋亡（P<0.01）。构建了一个包含 105 个候选靶点之间 578 个相互作用的 PPI 网络。最终，得出了 6 个核心靶点（TP53、CCND1、STAT3、LI1B、VEGFA 和 CCL2），其中 5 个核心靶点（TP53、CCND1、LI1B、VEGFA 和 CCL2）在 OC 和对照样本中差异表达，进一步用于 MR 分析。结果表明，CCND1 和 TP53 是 OC 的危险因素。分子对接分析表明，苦参碱与 TP53、CCND1 和 IL1B 具有良好的结合潜力。此外，苦参碱降低了 OC 细胞系中 CCND1 和 IL1B 的表达，同时升高了 P53 的表达。
我们确定了 6 个苦参碱相关靶点针对 OC，为苦参碱针对 OC 的治疗作用的分子机制提供了新的见解。这些发现为开发更有效和有针对性的 OC 治疗方法提供了有价值的指导。
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