Department of General Surgery, Mindong Hospital Affiliated to Fujian Medical University, Ningde, Fujian, China.
J Biochem Mol Toxicol. 2024 Nov;38(11):e70049. doi: 10.1002/jbt.70049.
Nodosin, a prominent diterpenoid derived from Rabdosia serra [Maxim] Hara extracts, exhibits notable antitumor activity in various cancers. However, its effect on hepatocellular carcinoma (HCC) and the underlying molecular mechanism remain inadequately understood, which is important for its clinical prescription. This study aims to reveal the mechanism through which nodosin exerts its effects, thereby providing further insights for its application. Nodosin was prepared in concentrations of 0, 0.2, 0.4, 0.6, 0.8, 1.0, and 2.0 μM. The effect of nodosin on the viability of SNU378 and HCCLM3 cells was evaluated using CCK8 and flow cytometry assays. Furthermore, the regulation of PI3K/AKT signaling was assessed by Western blot analysis. The results demonstrated that nodosin significantly suppressed the viability of SNU378 and HCCLM3 cells, yielding IC values of 0.890 and 0.766 μM, respectively. Notably, ERCC6L was downregulated in cells treated with nodosin. Overexpressing ERCC6L was found to reverse the proliferation inhibition and the apoptosis enhancement by nodosin in HCC cells. Additionally, ERCC6L was observed to mitigate the inhibitory effects of nodosin on PI3K/AKT signaling in both SNU378 and HCCLM3 cells. Conversely, the inhibition of PI3K/Akt signaling could counteract the effect of ERCC6L. Thus, the anti-proliferation effects of nodosin on HCC cells are mediated by the ERCC6L/PI3K/AKT axis.
从紫金牛属植物（Rabdosia serra [Maxim] Hara 提取物）中提取的角鲨烯是一种重要的二萜类化合物，在多种癌症中具有显著的抗肿瘤活性。然而，其对肝癌（HCC）的作用及其潜在的分子机制仍了解不足，这对于其临床应用非常重要。本研究旨在揭示角鲨烯发挥作用的机制，从而为其应用提供进一步的见解。用浓度为 0、0.2、0.4、0.6、0.8、1.0 和 2.0μM 的角鲨烯进行处理。通过 CCK8 和流式细胞术检测角鲨烯对 SNU378 和 HCCLM3 细胞活力的影响。此外，通过 Western blot 分析评估 PI3K/AKT 信号的调节。结果表明，角鲨烯显著抑制 SNU378 和 HCCLM3 细胞的活力，IC 值分别为 0.890 和 0.766μM。值得注意的是，角鲨烯处理的细胞中 ERCC6L 下调。过表达 ERCC6L 被发现可逆转角鲨烯对 HCC 细胞增殖抑制和凋亡增强的作用。此外，观察到 ERCC6L 减轻了角鲨烯对 SNU378 和 HCCLM3 细胞中 PI3K/AKT 信号的抑制作用。相反，PI3K/Akt 信号的抑制可以抵消 ERCC6L 的作用。因此，角鲨烯对角鲨烯对 HCC 细胞的增殖抑制作用是通过 ERCC6L/PI3K/AKT 轴介导的。
