JI-CJ002, a Natural Herbal Formula, Enhances the Antitumor Efficacy of FOLFOX in Colorectal Cancer by Suppressing the DDR Pathway.

BACKGROUND/AIM: Colorectal cancer (CRC) continues to pose substantial clinical challenges owing to the limited response and emergent resistance to standard chemotherapeutic regimens, including FOLFOX. The present investigation explored the antitumor efficacy of JI-CJ002, a standardized herbal formula consisting of Angelica gigas, Aconitum carmichaeli, and Zingiber officinale (2:1:3 ratio), and its combined effects with FOLFOX in in vitro settings.

MATERIALS AND

METHODS

Cytotoxic activities were assessed in HT29 and HCT116 human colorectal cancer cell lines by conducting MTT assays, Annexin V/7-AAD staining, and western blotting. Network pharmacology techniques were employed to identify common targets among JI-CJ002, FOLFOX, and CRC-associated gene profiles.

RESULTS

JI-CJ002 exhibited broad-spectrum cytotoxicity that was both time- and dose-dependent in HT29 and HCT116 cell lines. Network analysis identified 89 common targets predominantly involved in DNA repair, apoptosis, and chemoresistance pathways. The combination treatment led to a significant, synergistic reduction in cell viability and elevated apoptotic markers, including Annexin V/7-AAD positivity and cleaved PARP. Mechanistically, co-treatment inhibited ATM, ATR, p-CHK1, p-CHK2, p-Cdc2, and p-p53, while sustaining γ-H2AX accumulation, signifying persistent DNA damage and inadequate activation of cell cycle arrest checkpoints. Immunofluorescence revealed a further increase in γ-H2AX nuclear foci.

CONCLUSION

JI-CJ002 augments the therapeutic effect of FOLFOX by suppressing DNA damage response and inducing aberrant cell cycle progression, thereby supporting its development as a chemo-sensitizing agent for colorectal cancer therapy.