Ginsenoside Rh2 as a novel PIN1 inhibitor disrupting the cancer stem cell-like phenotype in non-small cell lung cancer

作者：Xiyu Liu, Zijun Mao, Jinglin Yang, Qianqian Zhu, Xinyi Dong, Gang Huang, Xizhong Shen, Lian Zhang, Hao Yang · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07318-0 · 被引用次数：5 · 研究领域：Ginseng Biological Effects and Applications、Signaling Pathways in Disease、Calcium signaling and nucleotide metabolism

BACKGROUND: The widespread issue of drug resistance remains a major obstacle in the treatment of lung cancer, particularly non-small cell lung cancer (NSCLC), making the development of novel adjuvant therapeutic strategies an urgent priority. Cancer stem cells (CSCs) are key drivers of drug resistance and metastasis, and the development of therapies targeting CSCs holds potential to overcome resistance to chemotherapy or targeted therapy in NSCLC. This study investigated the mechanisms by which ginsenoside Rh2 (G-Rh2) targeted CSCs and enhanced the efficacy of gefitinib (GF). METHODS: This study systematically examined the anti-tumor mechanisms of G-Rh2 using an integrated experimental approach. Flow cytometry, tumor sphere formation assays, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were employed to assess the effects of G-Rh2 on CSC formation and function. Protein microarray screening, combined with analysis of epithelial-mesenchymal transition (EMT) markers, lactate production assays, and co-immunoprecipitation (co-IP), were used to identify and validate the key molecular target of G-Rh2 as prolyl isomerase PIN1. Profiling of glycolytic metabolites demonstrated that the regulation of glucose metabolism by G-Rh2 is PIN1-dependent. Co-IP, immunofluorescence, and Western blotting were used to elucidate the mechanistic role of PIN1. Cell proliferation and apoptosis assays were conducted to evaluate the sensitizing effect of G-Rh2 on GF treatment...