Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Int J Biochem Cell Biol. 2018 Nov;104:55-65. doi: 10.1016/j.biocel.2018.09.003. Epub 2018 Sep 5.
The red raspberry (Rubus idaeus L.) is a common fruit worldwide and its extract has been found to inhibit the growth of many types of tumors, mainly because it is rich in bioactive phytochemicals. However, the mechanism underlying its anticancer activity in hepatocellular carcinoma (HCC) is not well understood. Herein, the aim of this study was to determine the effects of red raspberry phytochemicals on the proliferation of hepatocellular carcinoma cells and to elucidate its biochemical and molecular targets. CCK8 and colony formation, as well as flow cytometry assays, were employed to determine the effects of red raspberry extract (RRE) on cell proliferation and cell cycle distribution in HCC cells. Our results showed that RRE significantly inhibited cell proliferation and arrested cell cycle progression at the S phase in HCC cells. RRE increased the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) by reducing the methylation status of the PTEN gene promoter and inhibiting DNMT1 expression and regulated AKT signaling pathway. These findings show that red raspberry phytochemicals inhibit the proliferation of HCC cells by regulating PTEN/AKT signaling pathway, providing evidence that RRE may be used as a potential auxiliary therapy for patients with HCC.
红树莓（Rubus idaeus L.）是一种常见的世界性水果，其提取物已被发现能抑制多种类型肿瘤的生长，主要是因为它富含生物活性植物化学物质。然而，其在肝细胞癌（HCC）中的抗癌活性的机制尚不清楚。本研究旨在确定红树莓植物化学物质对肝癌细胞增殖的影响，并阐明其生化和分子靶点。CCK8 和集落形成以及流式细胞术检测用于确定红树莓提取物（RRE）对 HCC 细胞增殖和细胞周期分布的影响。我们的结果表明，RRE 可显著抑制 HCC 细胞的增殖，并在 S 期阻滞细胞周期进程。RRE 通过降低 PTEN 基因启动子的甲基化状态和抑制 DNMT1 表达来增加磷酸酶和张力蛋白同源物缺失的染色体 10（PTEN）的表达，并调节 AKT 信号通路。这些发现表明，红树莓植物化学物质通过调节 PTEN/AKT 信号通路抑制 HCC 细胞的增殖，为 RRE 可能被用作 HCC 患者的潜在辅助治疗提供了证据。
