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安纳托利亚蜂胶提取物通过调节AKT/mTOR通路增强顺铂对卵巢癌的疗效,并具有抗菌和抗生物膜活性。

Anatolian propolis extracts enhance cisplatin efficacy in ovarian cancer through AKT/mTOR pathway modulation and demonstrate antibacterial and antibiofilm activities.

作者信息

Erdoğan Esra, Özdem Berna, Çimentepe Özge Öztürk, Tekedereli İbrahim

机构信息

Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Harran University, Şanlıurfa, Türkiye.

Department of Medical Biology and Genetics, Faculty of Medicine, İnönü University, Malatya, Türkiye.

出版信息

Med Oncol. 2025 Jul 11;42(8):323. doi: 10.1007/s12032-025-02888-x.

Abstract

Propolis, a natural resinous substance rich in bioactive compounds, has been traditionally used for its therapeutic properties. This study investigates the cytotoxic and anticancer effects of Anatolian propolis on ovarian cancer cells, focusing on its modulation of the AKT/mTOR pathway and its ability to enhance cisplatin efficacy. Its antimicrobial and antibiofilm properties were also assessed, addressing infection risks in immunocompromised cancer patients. In epithelial ovarian cancer (A2780) cell line, apoptosis, cell cycle progression, and cell viability were evaluated using flow cytometric analysis, propidium iodide/annexin V staining, and MTS assay, respectively. The signaling pathways were analyzed using Western blotting. The IC value of propolis was determined as 0.342 ± 0.180 mg/mL in the A2780 cell line and 1.11 ± 0.31 mg/mL in the MCF-10A cell line. Apoptosis in the cells was evaluated using annexin V/PI staining and Caspase-3 expression via flow cytometry after treatment with varying concentrations of propolis and cisplatin. The combination of propolis at IC and cisplatin at IC demonstrated the highest apoptotic activity. Propolis treatment upregulated pro-apoptotic Bax while downregulating survival proteins (Bcl-2, mTOR/p-mTOR, and AKT/p-AKT) in A2780 cells, demonstrating AKT/mTOR pathway-mediated anticancer activity. Propolis exhibited potent antibacterial and antibiofilm activity against clinically relevant pathogens including MRSA and MDR E. coli, confirming its antimicrobial potential. Anatolian propolis demonstrates anticancer activity by modulating the AKT/mTOR pathway and enhancing cisplatin efficacy. Its antibacterial and antibiofilm properties further highlight its potential as a dual-function therapeutic agent, especially in cancer contexts where secondary infections are a common complication.

摘要

蜂胶是一种富含生物活性化合物的天然树脂状物质,传统上因其治疗特性而被使用。本研究调查了安纳托利亚蜂胶对卵巢癌细胞的细胞毒性和抗癌作用,重点关注其对AKT/mTOR通路的调节及其增强顺铂疗效的能力。还评估了其抗菌和抗生物膜特性,以解决免疫功能低下的癌症患者的感染风险。在上皮性卵巢癌(A2780)细胞系中,分别使用流式细胞术分析、碘化丙啶/膜联蛋白V染色和MTS测定法评估细胞凋亡、细胞周期进程和细胞活力。使用蛋白质免疫印迹法分析信号通路。在A2780细胞系中,蜂胶的IC值确定为0.342±0.180mg/mL,在MCF-10A细胞系中为1.11±0.31mg/mL。在用不同浓度的蜂胶和顺铂处理后,通过流式细胞术使用膜联蛋白V/PI染色和半胱天冬酶-3表达评估细胞凋亡。IC浓度的蜂胶与IC浓度的顺铂联合使用显示出最高的凋亡活性。蜂胶处理上调了促凋亡蛋白Bax,同时下调了A2780细胞中的存活蛋白(Bcl-2、mTOR/p-mTOR和AKT/p-AKT),证明了AKT/mTOR通路介导的抗癌活性。蜂胶对包括耐甲氧西林金黄色葡萄球菌和多重耐药大肠杆菌在内的临床相关病原体表现出强大的抗菌和抗生物膜活性,证实了其抗菌潜力。安纳托利亚蜂胶通过调节AKT/mTOR通路和增强顺铂疗效表现出抗癌活性。其抗菌和抗生物膜特性进一步突出了其作为双功能治疗剂的潜力,特别是在继发性感染是常见并发症的癌症情况下。

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