Induction of ferroptosis in oxaliplatin-resistant colorectal cancer cells by extract from Planch radix.

BACKGROUND

Colorectal cancer (CRC) is the third most common cancer worldwide, and there is growing number of reports on the emergence of chemoresistance among patients with CRC. Oxaliplatin, a common chemotherapeutic agent used to treat CRC, has been linked to the emergence of drug-resistant tumor cells. While traditional Chinese medicines have gained attention for their multi-target anticancer properties, Planch radix, despite its documented anti-inflammatory and hepatoprotective effects, remains unexplored in the context of oxaliplatin resistance modulation. This study aims to investigate whether Planch radix extract can reverse oxaliplatin resistance in CRC cells and determine its mechanistic relationship with ferroptosis-an iron-dependent form of regulated cell death implicated in chemoresistance.

METHODS

Oxaliplatin-resistant HT29 CRC cells were generated by increasing the concentration of oxaliplatin in the culture media. Cell viability was measured via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium-bromide) assay, while proliferation was assessed via wound healing assays. Gene expression was determined with quantitative polymerase chain reaction and Western blotting. Extract from Planch radix was achieved by hydrophilic extraction.

RESULTS

Treatment with Planch radix extract significantly inhibited the overgrowth of oxaliplatin-resistant HT29 cells, suggesting a potential reversal of chemoresistance. The extract induced ferroptosis, a type of programmed cell death dependent on iron and characterized by lipid peroxidation in oxaliplatin-resistant HT29 cells. The extract modified the expression of several key genes and proteins associated with chemoresistance and cell survival, including ubiquitin-specific-processing protease 7 (), wild-type tumor suppressor protein 53 (), and transferrin receptor 1 (). Changes were observed at both the messenger RNA and protein levels, indicating a direct regulatory effect.

CONCLUSIONS

Planch radix extract effectively reverses oxaliplatin resistance in CRC cells by inducing ferroptosis and modulating the expression of crucial genes including as , wild-type , and . These findings suggest that this traditional Chinese medicine could be a promising therapeutic agent to overcome chemoresistance in CRC.