2. Academic Validation
  3. Dioscin reduced chemoresistance for colon cancer and analysis of sensitizing targets

Dioscin reduced chemoresistance for colon cancer and analysis of sensitizing targets

  • Biochem Biophys Res Commun. 2022 Nov 11;638:94-102. doi: 10.1016/j.bbrc.2022.10.104.
Ruixue Li 1,  Jianyan Qin 2,  Ziyuan Wang 3,  Fenghong Lv 4,  Jiasen Guo 5,  Hong Zhu 6,  Youguang Huang 7
Affiliations

Affiliations

  • 1 Yunnan Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
  • 2 Yunnan Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
  • 3 Yunnan Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
  • 4 Yunnan Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
  • 5 Yunnan Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
  • 6 First Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
  • 7 Yunnan Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
PMID: 36442237 DOI: 10.1016/j.bbrc.2022.10.104
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.

Keywords

Chemotherapy resistance; Colon cancer; Dioscin; Drug target; Sensitization mechanism.

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