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Objective <p>Hepatocellular carcinoma (HCC) remains a therapeutic challenge with limited treatment options. This study investigated the anti-tumor potential of bergenin, a bioactive acylated iridoid glycoside, against HCC and elucidated its underlying molecular mechanisms.</p> Methods <p>We systematically evaluated bergenin’s effects using: (1) in vitro functional assays including CCK-8 viability, colony formation, TUNEL, flow cytometry, wound healing, and transwell assays; (2) molecular analyses of apoptosis markers (cleaved caspase-3/-9), metastasis-related proteins (MMP-2/-9), and key signaling pathways; and (3) in vivo xenograft models assessing tumor growth inhibition.</p> Results <p>Bergenin demonstrated potent anti-HCC activity through multiple mechanisms: (1) dose-dependently inhibiting cell proliferation and colony formation; (2) inducing apoptosis via caspase-3/-9 activation; (3) suppressing migration and invasion through MMP-2/-9 downregulation; and (4) significantly inhibiting tumor growth in vivo. Mechanistically, bergenin concurrently inhibited both PI3K/Akt/mTOR and MAPK/ERK signaling pathways in vitro and in vivo.</p> Conclusion <p>Our findings demonstrate that bergenin exerts anti-HCC effects by simultaneously targeting proliferation, apoptosis, and metastasis through dual inhibition of oncogenic PI3K/Akt/mTOR and MAPK/ERK pathways.</p>

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Bergenin exerts anti-cancer activity in hepatocellular carcinoma via the PI3K/Akt/mTOR and MAPK/ERK pathways

  • 期刊论文

  • 发表日期：

    2025年7月5日

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  • Guangrui Lu,
  • Xun Zhuang,
  • Chunrong Wang,
  • Zhenghui Ge,
  • Mengjie Wu,
  • Mengjiao Chen,
  • Zhen Chen,
  • Jianghong Hu,
  • Haoqing Zhai

摘要

Objective

Hepatocellular carcinoma (HCC) remains a therapeutic challenge with limited treatment options. This study investigated the anti-tumor potential of bergenin, a bioactive acylated iridoid glycoside, against HCC and elucidated its underlying molecular mechanisms.

Methods

We systematically evaluated bergenin’s effects using: (1) in vitro functional assays including CCK-8 viability, colony formation, TUNEL, flow cytometry, wound healing, and transwell assays; (2) molecular analyses of apoptosis markers (cleaved caspase-3/-9), metastasis-related proteins (MMP-2/-9), and key signaling pathways; and (3) in vivo xenograft models assessing tumor growth inhibition.

Results

Bergenin demonstrated potent anti-HCC activity through multiple mechanisms: (1) dose-dependently inhibiting cell proliferation and colony formation; (2) inducing apoptosis via caspase-3/-9 activation; (3) suppressing migration and invasion through MMP-2/-9 downregulation; and (4) significantly inhibiting tumor growth in vivo. Mechanistically, bergenin concurrently inhibited both PI3K/Akt/mTOR and MAPK/ERK signaling pathways in vitro and in vivo.

Conclusion

Our findings demonstrate that bergenin exerts anti-HCC effects by simultaneously targeting proliferation, apoptosis, and metastasis through dual inhibition of oncogenic PI3K/Akt/mTOR and MAPK/ERK pathways.