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<p>High levels of DNA damage repair (DDR) can promote the survival, immune evasion, and drug resistance of colorectal cancer (CRC) cells, consequently facilitating the advancement of CRC. This study was designed to investigate the inhibitory effect of berberine (BBR) on CRC progression and the underlying mechanism involving DDR regulation, to provide a novel theoretical basis for clinical CRC treatment. First, we found that BBR demonstrated a dose-dependent inhibition of the viability of CRC cells. BBR promoted apoptosis and suppressed the DDR in CRC cells by upregulating SOX17. Overexpression of SOX17 restrained CRC cell viability and facilitated cell apoptosis. BBR inhibited the DDR of CRC cells by inactivating the β-catenin/TCF4 pathway through the regulation of SOX17. Furthermore, TCF4 transcriptionally activated PIM3 expression. Knockdown of SOX17 partially eliminated the suppressive effects of BBR on CRC cell viability and DDR. Conversely, PIM3 silencing reversed the effects of SOX17 knockdown. In conclusion, we demonstrated BBR inhibits DDR in CRC cells via mediating the SOX17/TCF4/PIM3 axis, thereby blocking CRC progression. This regulatory axis serves as a potential therapeutic target for CRC, and BBR holds promising application prospects as a DDR inhibitor in CRC clinical intervention.</p>

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Berberine impedes the DNA damage repair to inhibit colorectal cancer by regulating the SOX17/TCF4/PIM3 axis

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Fan Hu,
  • Wei Wang,
  • Mei Li,
  • Qian Shi,
  • Junjie Que,
  • Pan Huang

摘要

High levels of DNA damage repair (DDR) can promote the survival, immune evasion, and drug resistance of colorectal cancer (CRC) cells, consequently facilitating the advancement of CRC. This study was designed to investigate the inhibitory effect of berberine (BBR) on CRC progression and the underlying mechanism involving DDR regulation, to provide a novel theoretical basis for clinical CRC treatment. First, we found that BBR demonstrated a dose-dependent inhibition of the viability of CRC cells. BBR promoted apoptosis and suppressed the DDR in CRC cells by upregulating SOX17. Overexpression of SOX17 restrained CRC cell viability and facilitated cell apoptosis. BBR inhibited the DDR of CRC cells by inactivating the β-catenin/TCF4 pathway through the regulation of SOX17. Furthermore, TCF4 transcriptionally activated PIM3 expression. Knockdown of SOX17 partially eliminated the suppressive effects of BBR on CRC cell viability and DDR. Conversely, PIM3 silencing reversed the effects of SOX17 knockdown. In conclusion, we demonstrated BBR inhibits DDR in CRC cells via mediating the SOX17/TCF4/PIM3 axis, thereby blocking CRC progression. This regulatory axis serves as a potential therapeutic target for CRC, and BBR holds promising application prospects as a DDR inhibitor in CRC clinical intervention.