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 IC50 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.
Keywords: ERCC6L; PI3K/AKT signaling; Rabdosia serra [Maxim] Hara; cell apoptosis; cell proliferation.
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