Affiliation:
1. Department of Nephrology Chongqing Hospital of Traditional Chinese Medicine Chongqing China
2. Department of Research and Development Chongqing Precision Medical Industry Technology Research Institute Chongqing China
3. Division of Cardiology The First Affiliated Hospital of Chongqing Medical University Chongqing China
4. Department of Oncology Chongqing Hospital of Traditional Chinese Medicine Chongqing China
5. Department of Rehabilitation Medicine Chongqing Hospital of Traditional Chinese Medicine Chongqing China
Abstract
AbstractWhile pachymic acid (PA), a key component of Poria cocos (Schw.), has demonstrated anti‐tumor effects in lung, breast, and pancreatic cancers, its impact on renal cell carcinoma (RCC) is unclear. This study evaluated the effect of PA on proliferation, migration, and apoptosis in human renal cancer A498 and ACHN cells as well as in cancer xenograft mice using wound scratch test, Western blotting, and co‐immunoprecipitation assays. In a dose‐ and time‐dependent manner, PA exhibited significant inhibition of RCC cell proliferation, migration, and invasion, accompanied by the induction of apoptosis. Additionally, PA upregulated the expression of tumor protein p53‐inducible nuclear protein 2 (TP53INP2) and tumor necrosis factor receptor‐associated factor 6 (TRAF6), which were downregulated in renal papillary and chromophobe carcinoma, resulting in inhibited tumor growth in mice. PA treatment elevated cleaved‐caspase 3 and 8, and PARP levels, and facilitated TP53INP2 and TRAF6 binding to caspase 8, promoting its ubiquitination. Molecular docking revealed interactions between PA and TP53INP2, TRAF6. In summary, PA inhibits RCC development by upregulating TP53INP2 and promoting TRAF6‐induced caspase 8 ubiquitination, activating apoptotic pathways.