Chinese medicine
Astragali Radix-Curcumae Rhizoma synergistically potentiates 5-fluorouracil antitumor efficacy in colorectal cancer by disrupting DNA repair-cell cycle coordination
By Wang S, Huang K, Cheng Y and 7 others.
Abstract
Background
Astragali Radix (HQ) and Curcumae Rhizoma (EZ), collectively termed AC, are commonly used as an herb pair in Traditional Chinese Medicine (TCM) for colorectal cancer (CRC). Although AC has been used as an adjuvant to chemotherapy, the molecular basis by which it enhances the efficacy of 5-fluorouracil (5-FU) remains incompletely defined.
Methods
The antitumor effect of AC alone and in combination with 5-FU was evaluated in a HCT116 xenograft mouse model and in CRC cell lines with different genetic backgrounds. Potential systemic toxicity was assessed using serum biochemical markers. Transcriptomic changes induced by AC were analyzed by RNA sequencing and integrated with network pharmacology and The Gene Expression Omnibus (GEO) (GSE17536, GSE17537, GSE41258, GSE20916). Key targets were validated by Western blotting and immunofluorescence. Cell viability, drug interaction, apoptosis, cell-cycle distribution and DNA damage were assessed using CCK-8 assays, Synergy Finder analysis, flow cytometry, and γ-H2AX staining. Bioavailable AC-derived constituents were characterized by UPLC-QTOF-MS, and candidate active compounds were further evaluated by molecular docking, molecular dynamics simulation, cellular thermal shift assay, and functional validation.