Molecular biology reports · 2026
Filgotinib induces apoptosis in colorectal cancer cells by activating the p53 signaling pathway.
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.
Zhou Ying, Li Zhen, Zhao Yanyang, Li Chenmeng, Ye Huiming
Аннотация
BACKGROUND: Colorectal cancer remains a significant health challenge. Filgotinib is a selective JAK1 inhibitor approved for the treatment of inflammatory diseases. However, its anti-tumor effects and underlying mechanisms in colorectal cancer (CRC) remain unexplored.
METHODS AND RESULTS: In this study, cell viability and proliferation were assessed by CCK‑8, crystal violet, and EdU assays. Mitochondrial membrane potential was evaluated using JC‑1 staining. Transcriptome sequencing (RNA‑seq) was performed on RKO cells treated with Filgotinib, followed by GO and KEGG pathway enrichment analyses. Protein expression was examined by Western blot. The effect of Filgotinib was further validated in three human CRC patient‑derived organoids (PDOs). Filgotinib at concentrations near the IC50 (14 µM for HCT116, 10 µM for RKO, 14 µM for LoVo) reduced cell viability and proliferation, as shown by CCK‑8, crystal violet, and EdU assays. Western blot analysis confirmed reduced JAK1 and STAT3 protein expression after Filgotinib treatment compared with the control. Filgotinib induced mitochondrial‑dependent apoptosis, evidenced by increased green fluorescence in the JC‑1 assay. Transcriptomic profiling of RKO cells treated with 10 µM Filgotinib for 48 h identified 1,151 upregulated and 862 downregulated genes. GO analysis revealed enrichment in terms related to chromatin structure, nucleotide binding, and metabolic processes. KEGG analysis highlighted activation of the p53 signaling pathway and suppression of oncogenic pathways including VEGF and TNF signaling. At the protein level, Filgotinib treatment increased the expression of p21 (a key p53 pathway effector) and cleaved caspase-3 compared with the control group. Furthermore, treatment of human CRC-derived PDOs with Filgotinib (≥ 10 µM) for 48 h resulted in organoid disintegration.
CONCLUSIONS: Our study demonstrates that Filgotinib exerts direct anti-tumor effects in CRC by triggering apoptosis, activating the p53 pathway, and inhibiting pro-survival VEGF and TNF pathways. These findings support its potential as a targeted therapeutic agent for CRC.
METHODS AND RESULTS: In this study, cell viability and proliferation were assessed by CCK‑8, crystal violet, and EdU assays. Mitochondrial membrane potential was evaluated using JC‑1 staining. Transcriptome sequencing (RNA‑seq) was performed on RKO cells treated with Filgotinib, followed by GO and KEGG pathway enrichment analyses. Protein expression was examined by Western blot. The effect of Filgotinib was further validated in three human CRC patient‑derived organoids (PDOs). Filgotinib at concentrations near the IC50 (14 µM for HCT116, 10 µM for RKO, 14 µM for LoVo) reduced cell viability and proliferation, as shown by CCK‑8, crystal violet, and EdU assays. Western blot analysis confirmed reduced JAK1 and STAT3 protein expression after Filgotinib treatment compared with the control. Filgotinib induced mitochondrial‑dependent apoptosis, evidenced by increased green fluorescence in the JC‑1 assay. Transcriptomic profiling of RKO cells treated with 10 µM Filgotinib for 48 h identified 1,151 upregulated and 862 downregulated genes. GO analysis revealed enrichment in terms related to chromatin structure, nucleotide binding, and metabolic processes. KEGG analysis highlighted activation of the p53 signaling pathway and suppression of oncogenic pathways including VEGF and TNF signaling. At the protein level, Filgotinib treatment increased the expression of p21 (a key p53 pathway effector) and cleaved caspase-3 compared with the control group. Furthermore, treatment of human CRC-derived PDOs with Filgotinib (≥ 10 µM) for 48 h resulted in organoid disintegration.
CONCLUSIONS: Our study demonstrates that Filgotinib exerts direct anti-tumor effects in CRC by triggering apoptosis, activating the p53 pathway, and inhibiting pro-survival VEGF and TNF pathways. These findings support its potential as a targeted therapeutic agent for CRC.