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Bergenin exerts anti-cancer activity in hepatocellular carcinoma via the PI3K/Akt/mTOR and MAPK/ERK pathways
Guangrui Lu1, Xun Zhuang2, Chunrong Wang2
1Department of Hepatobiliary Pancreatic Surgery, The First College of Clinical Medical Science, Yichang Central People's Hospital, China Three Gorges University, Yichang, 443100, People's Republic of China.
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.
Insights
Bergenin shows promise in fighting liver cancer (Hepatocellular carcinoma, HCC). It inhibits tumor growth, triggers cancer cell death, and reduces spread by targeting key growth pathways.
Area of Science:
- Hepatocellular Carcinoma (HCC) Research
- Natural Product Drug Discovery
- Molecular Oncology
Background:
- Hepatocellular carcinoma (HCC) presents significant therapeutic challenges due to limited effective treatment options.
- Bergenin, a natural bioactive compound, has potential as an anti-cancer agent.
- Understanding bergenin's molecular mechanisms against HCC is crucial for therapeutic development.
Purpose of the Study:
- To investigate the anti-tumor effects of bergenin on Hepatocellular Carcinoma (HCC).
- To elucidate the molecular mechanisms underlying bergenin's anti-HCC activity.
- To evaluate bergenin's efficacy in both in vitro and in vivo models.
Main Methods:
- In vitro assays: CCK-8 viability, colony formation, TUNEL, flow cytometry, wound healing, and transwell assays.
- Molecular analyses: apoptosis markers (caspase-3/-9), metastasis proteins (MMP-2/-9), and signaling pathways (PI3K/Akt/mTOR, MAPK/ERK).
- In vivo studies: Xenograft models to assess tumor growth inhibition.
Main Results:
- Bergenin significantly inhibited HCC cell proliferation and colony formation in a dose-dependent manner.
- Apoptosis was induced by bergenin through caspase-3/-9 activation.
- Cell migration and invasion were suppressed via downregulation of MMP-2/-9.
- Tumor growth was significantly inhibited in vivo.
- Bergenin concurrently inhibited PI3K/Akt/mTOR and MAPK/ERK signaling pathways.
Conclusions:
- Bergenin demonstrates potent anti-HCC activity by inhibiting proliferation, inducing apoptosis, and suppressing metastasis.
- The anti-tumor effects are mediated through the dual inhibition of the PI3K/Akt/mTOR and MAPK/ERK signaling pathways.
- Bergenin represents a promising therapeutic candidate for Hepatocellular Carcinoma treatment.
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