Frontiers in pharmacology · 2025
Cryptotanshinone targets tumor-immune-microbiome axis to suppress colorectal cancer.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yang Zhenya, Zhou Mengting, Luo Fenglin, Feng Shiqi, Tan Yu, Wang Qiqian, Cheng Zeneng, Tan Ruirong, Li Rui
Аннотация
BACKGROUND: Colorectal cancer (CRC) progression involves complex interactions between tumor cells, immune evasion, and metabolic reprogramming. Cryptotanshinone (CTS), a bioactive diterpenoid from Salvia miltiorrhiza, has demonstrated anticancer potential, but its integrated effects on CRC remain unclear.
METHODS: We employed both in vitro and in vivo models to evaluate the therapeutic effects and mechanism of CTS. Using MC38 cells and mouse-derived CRC organoids, we assessed its impact on proliferation and apoptosis through CCK-8, clonogenic, and Annexin V/PI assays. For vivo evaluation, a murine AOM/DSS-induced CRC model was established and administered CTS via intraperitoneal injection for 8 weeks. Comprehensive analyses included histopathology, immune profiling by flow cytometry, 16S rRNA sequencing of gut microbiota, and LC-MS-based metabolomics.
RESULTS: CTS exerted potent anti-CRC effects, suppressing tumor cell proliferation and inducing apoptosis in vitro. In AOM/DSS-induced mice, CTS significantly inhibited tumor growth, ameliorated colon shortening and pathological damage, and reduced inflammation. Mechanistically, CTS alleviated T cell exhaustion, reversed metabolic dysregulation, and restored gut microbiota community structure.
CONCLUSION: CTS effectively suppresses CRC progression. Its efficacy is associated with the coordinated modulation of the tumor-immune-microbiome axis, involving direct cytotoxicity, reduced PD-1+ T cell levels, and restructuring of the gut microbial community. These results highlight CTS as a promising multi-faceted therapeutic candidate and provide a preclinical rationale for its further development.
METHODS: We employed both in vitro and in vivo models to evaluate the therapeutic effects and mechanism of CTS. Using MC38 cells and mouse-derived CRC organoids, we assessed its impact on proliferation and apoptosis through CCK-8, clonogenic, and Annexin V/PI assays. For vivo evaluation, a murine AOM/DSS-induced CRC model was established and administered CTS via intraperitoneal injection for 8 weeks. Comprehensive analyses included histopathology, immune profiling by flow cytometry, 16S rRNA sequencing of gut microbiota, and LC-MS-based metabolomics.
RESULTS: CTS exerted potent anti-CRC effects, suppressing tumor cell proliferation and inducing apoptosis in vitro. In AOM/DSS-induced mice, CTS significantly inhibited tumor growth, ameliorated colon shortening and pathological damage, and reduced inflammation. Mechanistically, CTS alleviated T cell exhaustion, reversed metabolic dysregulation, and restored gut microbiota community structure.
CONCLUSION: CTS effectively suppresses CRC progression. Its efficacy is associated with the coordinated modulation of the tumor-immune-microbiome axis, involving direct cytotoxicity, reduced PD-1+ T cell levels, and restructuring of the gut microbial community. These results highlight CTS as a promising multi-faceted therapeutic candidate and provide a preclinical rationale for its further development.