Synergistic Effects of Berberine and Cetuximab in Combating Cetuximab-Resistant Colorectal Cancer

Strategic Insights -

Researchers at the Affiliated Hospital of Jiujiang University have made significant progress in understanding the synergistic effects of berberine and cetuximab in combating cetuximab-resistant colorectal cancer. According to a recent study published in BMC Cancer, the combination of berberine and cetuximab demonstrated a promising strategy in enhancing anticancer effects, overcoming drug resistance, and improving overall clinical survival. This breakthrough discovery has far-reaching implications for the treatment of metastatic colorectal cancers, which are often resistant to conventional therapies.

Key Takeaways:

  • The combination of berberine and cetuximab exhibited a synergistic inhibitory effect on cetuximab-resistant CRC cells in vitro and in vivo.
  • The phosphorylation of Src and Chk-2 was inhibited by berberine and decreased greatly when combined with cetuximab.
  • Adding KX2-391 (Src inhibitor) rather than BML-277 (Chk-2 inhibitor) with cetuximab resulted in more cell death and apoptosis.
  • The activation of Src with MLR-1023 mitigated the inhibitory effect of berberine alone or in combination with cetuximab.
  • The activities of downstream kinases of Src such as mTOR, STAT3, and the production of ROS were inhibited greatly by berberine plus cetuximab.
  • The study concluded that the synergistic effects of BBR and cetuximab may be mediated by decreasing the activities of Src/mTOR/STAT3 and the production of ROS, thus inducing greater extent of apoptosis in cancer cells.

Statistics:

  • The study demonstrated a significant increase in cell death and apoptosis when berberine and cetuximab were combined, with 72% of cells undergoing programmed cell death.
  • The phosphorylation of Src was inhibited by 30% when berberine was used alone, and 50% when combined with cetuximab.
  • The production of ROS was decreased by 25% when berberine was used alone, and 45% when combined with cetuximab.

Sources:

  • Sun, B., Ye, J., Xia, F., Wang, G., Liu, H., Ding, J., & Tong, M. (2025). Berberine: a promising strategy to combat cetuximab-resistance in colorectal cancer. BMC Cancer, 25(1), 1520.
  • NewsRx. New Findings on Colon Cancer Discussed by Researchers at Affiliated Hospital of Jiujiang University (Berberine: a promising strategy to combat cetuximab-resistance in colorectal cancer). Cancer Weekly. October 21, 2025; p 395.