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• W3136196973 endingPage "153553" @default.
• W3136196973 startingPage "153553" @default.
• W3136196973 abstract "Colorectal cancer (CRC) is one of the most malignant tumors worldwide with poor prognosis and low survival rate. Since the clinical efficacy of the commonly used 5-fluorouracil (5-FU) based chemotherapy in CRC patients is limited because of its intolerable adverse effects, there is an urgent need to explore agents that can enhance the anti-cancer activity of 5-FU, reduce adverse effects and prevent resistance. This study aims to investigate Tenacissoside G (TG)’s synergistic potentiation with 5-FU in inhibitory activity to colorectal cancer cells. The anti-proliferation effect of TG on 5 colorectal cancer cell lines was assessed by CCK-8 assay. The isobologram analysis and combination index methods were used to detect the synergistic effect of TG and 5-FU by the CompuSyn software using the T.C. Chou Method. The effects of TG/5-FU combination on cell cycle distribution and apoptosis induction were detected by flow cytometry. DNA damage degrees of cells treated with TG, 5-FU and their combination were evaluated by the alkaline comet assay. Protein expression regulated by the TG/5-FU combination was investigated by western blotting. Furthermore, a xenograft mouse model was established to investigate the synergistic anti-tumor effect in vivo. In this work, we observed a dose-dependent growth inhibitory activity and cell cycle arrest induction of TG, a monomeric substance originated from Marsdenia tenacissima (Roxb.) Wight et Arn, in colorectal cancer cells. It was found that TG potentiated the anticancer effects of 5-FU with a synergism for the first time. And the co-treatment effects were also validated by in vivo experiments. The underlying mechanisms involved in the synergistic effects were probably included: (1) increased activation of caspase cascade; (2) enhancement of DNA damage degree and (3) induction of p53 phosphorylation at Serine 46. TG potentiated 5-FU's inhibitory activity to human colorectal cancer through arresting cell cycle progression and inducing p53-mediated apoptosis, which may present a novel strategy in CRC therapies and contribute to the optimizing clinical application of 5-FU." @default.
• W3136196973 created "2021-03-29" @default.
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• W3136196973 date "2021-06-01" @default.
• W3136196973 modified "2023-09-26" @default.
• W3136196973 title "Tenacissoside G synergistically potentiates inhibitory effects of 5-fluorouracil to human colorectal cancer" @default.
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• W3136196973 doi "https://doi.org/10.1016/j.phymed.2021.153553" @default.
• W3136196973 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33906076" @default.
• W3136196973 hasPublicationYear "2021" @default.
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