Dioscin reduced chemoresistance for colon cancer and analysis of sensitizing targets

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Chemotherapy resistance is a major challenge in advanced colon cancer treatment.
• Traditional medicine compounds like dioscin (DIO) show potential for chemosensitization.

Purpose of the Study:

• To investigate the chemosensitizing effect of dioscin (DIO) in combination with Oxaliplatin (L-OHP) and 5-fluorouracil (5-Fu) for colon cancer.
• To explore the underlying molecular mechanisms of DIO-enhanced chemotherapy.

Main Methods:

• In vitro studies using HCT116 colon cancer cells treated with DIO, L-OHP, and 5-Fu.
• In vivo xenograft mouse models to assess efficacy and toxicity.
• mRNA sequencing and network pharmacological analysis to identify molecular targets.

Main Results:

• Co-treatment with DIO, L-OHP, and 5-Fu significantly inhibited colon cancer cell proliferation, colony formation, and migration.
• DIO-L-OHP treatment increased apoptosis and induced cell-cycle arrest at G0/G1 and G2/M phases.
• DIO-assisted L-OHP demonstrated significant tumor growth inhibition in xenograft models with low toxicity.
• Network analysis identified FAS, CDKN1A, ABCA1, and PPARA as key targets involved in cell cycle regulation and apoptosis.

Conclusions:

• Dioscin enhances the sensitivity of colon cancer cells to Oxaliplatin and 5-fluorouracil.
• DIO-assisted chemotherapy effectively inhibits tumor growth and exhibits low toxicity.
• The Notch pathway and regulation of cell cycle/apoptosis are implicated in DIO's chemosensitizing mechanism.