Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Apoptosis. 2023 Oct;28(9-10):1346-1356. doi: 10.1007/s10495-023-01863-z. Epub 2023 Jun 20.
Hepatocellular carcinoma (HCC) is one of the most critical cancers; thus, novel therapeutical regimens are of great need. In this study, we investigated the effects of umbilical cord mesenchymal stem cells (UC-MSCs) derived exosomes on HepG2 cell line, and the underlying mechanism to control HCC proliferation, to identify the potential clinical role of exosomes as a novel molecular therapeutic target. Proliferation, apoptosis, and angiogenesis effects were assessed together with the cell viability evaluation by MTT assay in HepG2 cells at 24/48 h. with or without UC-MSCs-derived exosomes. Gene expressions of TNF-α, caspase-3, VEGF, stromal cell-derived factor-1 (SDF-1), and CX chemokine receptor-4 (CXCR-4) were measured by quantitative real-time PCR technique. Expression of sirtuin-1 (SIRT-1) protein was detected by western blot. Treatment of HepG2 cells with UC-MSCs-derived exosomes for 24 and 48 h. demonstrated a significant reduction of cells survival compared to the control group (p < 0.05). The SIRT-1 protein, and VEGF, SDF-1, CXCR-4 expression levels were significantly lower, TNF-α and caspase-3 expression levels were significantly higher in exosomal-treated HepG2 cells for 24 and 48 h. than those in the control group. Moreover, our findings documented that the anti-proliferative, apoptotic, and anti-angiogenic effects were achieved in a time-dependent manner in which more effects were determined after 48 h supplementation compared to 24 h (p < 0.05). UC-MSCs-derived exosomes exert anticarcinogenic molecular effects on HepG2 cells through the involvement of SIRT-1, SDF-1, and CXCR-4. Hence, exosomes would be a potential novel therapy regimen against HCC. Large-scale studies are recommended to verify this conclusion.
肝细胞癌 (HCC) 是最严重的癌症之一；因此，非常需要新的治疗方案。在这项研究中，我们研究了脐带间充质干细胞 (UC-MSCs) 衍生的外泌体对 HepG2 细胞系的影响及其控制 HCC 增殖的潜在机制，以确定外泌体作为一种新的分子治疗靶点的潜在临床作用。通过 MTT assay 评估 24/48 小时 HepG2 细胞的增殖、凋亡和血管生成作用以及细胞活力。用定量实时 PCR 技术测量 TNF-α、caspase-3、VEGF、基质细胞衍生因子-1 (SDF-1) 和 CX 趋化因子受体-4 (CXCR-4) 的基因表达。通过 Western blot 检测 SIRT-1 蛋白的表达。与对照组相比，HepG2 细胞用 UC-MSCs 衍生的外泌体处理 24 和 48 小时后，细胞存活率显著降低 (p<0.05)。与对照组相比，24 和 48 小时外泌体处理的 HepG2 细胞中的 SIRT-1 蛋白和 VEGF、SDF-1、CXCR-4 表达水平显著降低，TNF-α 和 caspase-3 表达水平显著升高。此外，我们的研究结果表明，这种抗增殖、凋亡和抗血管生成作用是在时间依赖性的方式下实现的，与 24 小时相比，48 小时补充后确定了更多的作用 (p<0.05)。UC-MSCs 衍生的外泌体通过 SIRT-1、SDF-1 和 CXCR-4 的参与对 HepG2 细胞发挥抗癌分子作用。因此，外泌体可能是一种针对 HCC 的潜在新型治疗方案。建议进行大规模研究来验证这一结论。
