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Background <p>HER2-positive breast cancer, known for its heterogeneity and complex molecular mechanisms, poses a significant therapeutic challenge. Lidocaine, a widely used local anesthetic, has recently been identified as a potential anticancer agent. This study investigates the effects of lidocaine on HER2-positive breast cancer proliferation and the underlying mechanisms.</p> Methods <p>The effects of lidocaine on cell proliferation, cell cycle distribution, and O-GlcNAcylation levels in AU565 and BT474 cells were assessed using CCK-8 assays, EdU incorporation assays, flow cytometry, and western blot analysis. Furthermore, the interaction between lidocaine and OGT was examined using molecular docking and co-immunoprecipitation (co-IP) experiments.</p> Results <p>Lidocaine was found to significantly inhibit cell viability and proliferation in AU565 and BT474 cells, inducing G0/G1 cell cycle arrest. Mechanistically, lidocaine was observed to downregulate O-GlcNAc transferase (OGT), consequently reducing global O-GlcNAcylation levels. We further demonstrated that OGT interacts with and stabilizes CCNL1 via O-GlcNAcylation, and this interaction is critical for CCNL1-mediated cancer cell proliferation. Notably, rescue experiments revealed that the overexpression of either OGT or CCNL1 could partially reverse the suppressive effects of lidocaine.</p> Conclusions <p>In conclusion, this study reveals a novel mechanism by which lidocaine inhibits HER2-positive breast cancer cell proliferation by targeting the OGT-CCNL1 axis, highlighting a potential therapeutic avenue for HER2-positive breast cancer.</p>

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Lidocaine suppresses HER2-positive breast cancer cell proliferation by targeting the OGT-CCNL1 axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月5日

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  • Yunfei Sun,
  • Bo Liu,
  • Xuan Zhang,
  • Chengqi Deng,
  • Nan Hu,
  • Yiqing Yin

摘要

Background

HER2-positive breast cancer, known for its heterogeneity and complex molecular mechanisms, poses a significant therapeutic challenge. Lidocaine, a widely used local anesthetic, has recently been identified as a potential anticancer agent. This study investigates the effects of lidocaine on HER2-positive breast cancer proliferation and the underlying mechanisms.

Methods

The effects of lidocaine on cell proliferation, cell cycle distribution, and O-GlcNAcylation levels in AU565 and BT474 cells were assessed using CCK-8 assays, EdU incorporation assays, flow cytometry, and western blot analysis. Furthermore, the interaction between lidocaine and OGT was examined using molecular docking and co-immunoprecipitation (co-IP) experiments.

Results

Lidocaine was found to significantly inhibit cell viability and proliferation in AU565 and BT474 cells, inducing G0/G1 cell cycle arrest. Mechanistically, lidocaine was observed to downregulate O-GlcNAc transferase (OGT), consequently reducing global O-GlcNAcylation levels. We further demonstrated that OGT interacts with and stabilizes CCNL1 via O-GlcNAcylation, and this interaction is critical for CCNL1-mediated cancer cell proliferation. Notably, rescue experiments revealed that the overexpression of either OGT or CCNL1 could partially reverse the suppressive effects of lidocaine.

Conclusions

In conclusion, this study reveals a novel mechanism by which lidocaine inhibits HER2-positive breast cancer cell proliferation by targeting the OGT-CCNL1 axis, highlighting a potential therapeutic avenue for HER2-positive breast cancer.