Dioscin reduced chemoresistance for colon cancer and analysis of sensitizing targets

Abstract

Chemotherapy resistance is the primary cause of high mortality in patients with advanced colon cancer. The combination of small molecule compound dioscin (DIO) and traditional medicine may have a chemosensitizing effect. In this study, we reported that DIO, in combination with Oxaliplatin (L-OHP) and 5-fluorouracil (5-Fu), can effectively inhibit colon cancer cell proliferation, and co-treatment was positively related to the DIO concentration. HCT116 co-treatment with 6.4 μM L-OHP and 0.8 μM DIO significantly reduced colony formation and migration, increased apoptosis, and cell-cycle arrest in the G0/G1 and G2/M phase. DIO-assisted L-OHP significantly inhibited the xenograft model growth and exhibited low toxicity.The mRNA-sequencing combined with network pharmacological analysis suggested that the DIO sensitivity may be related to the active targets FAS, CDKN1A, ABCA1, and PPARA, which are primarily involved in regulating the cell cycle and apoptosis. Finally, our experiments suggest that DIO may enhance the L-OHP sensitivity by regulating the cell cycle through the Notch pathway.