Natural compounds, including Poria acid (PAC), tetrandrine (Tet), Dendrobine, gallic acid (GA) and Eupatilin, can target the PI3K/AKT signaling pathway (e.g., PAC/Tet blocks NF-κB activation, and Dendrobine downregulates phosphorylated protein, GA enhances autophagy and eupatilin-induced apoptosis), synergistically inhibit the proliferation, invasion and migration of RCC cells (Yang H. et al., 2024; Jia et al., 2025; Chen et al., 2017; Zhang T. et al., 2024; Zhong et al., 2016). The gene discussed is AKT1; the disease is renal cell adenocarcinoma.