Oridonin derivative DLC13 targeting proliferating cell nuclear antigen to overcome oxaliplatin resistance in colorectal cancer - PubMed
7 hours ago
- #PCNA
- #oxaliplatin resistance
- #colorectal cancer
- Oridonin derivative DLC13 shows enhanced potency against colorectal cancer (CRC) cell lines compared to its parent compound.
- DLC13 inhibits DNA damage repair, cell cycle progression, stemness, and migration in CRC cells.
- DLC13 can reverse oxaliplatin (OXA) resistance in CRC by suppressing abnormal gene expression driven by OXA.
- Proliferating cell nuclear antigen (PCNA) is identified as a direct target of DLC13, crucial for overcoming OXA resistance.
- DLC13 promotes K48-linked polyubiquitination and degradation of PCNA, inhibiting its biological functions.
- Combination therapy with DLC13 and OXA presents a promising strategy for refractory CRC treatment.