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Fangchinoline induces gallbladder cancer cell apoptosis by suppressing PI3K/Akt/XIAP axis
Jiandong Li1,2,3, Wenda Cen2,3,4, Chenhao Tong1,2,3
1Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Abstract:
Gallbladder cancer (GBC) is the most common biliary tract malignancy with a dismal prognosis. The development of new drugs may help to improve prognosis. This study found that fangchinoline, a bisbenzylisoquinoline alkaloids, inhibited the proliferation and clone formation of GBC cells in a dose-dependent manner. Moreover, Hoechst staining, TUNEL assays, and flow cytometry demonstrated that fangchinoline effectively induced apoptosis in GBC cells. Further studies found that an anti-apoptotic pathway, the PI3K/Akt/XIAP axis, was significantly inhibited in GBC cells after treating with fangchinoline. Finally, we confirmed that fangchinoline restrained xenograft tumor growth in vivo. Our findings indicate that fangchinoline can be considered a potential drug for GBC treatment.
Insights
Fangchinoline, a natural compound, effectively inhibits gallbladder cancer (GBC) cell growth and promotes apoptosis. This study suggests fangchinoline as a promising new drug candidate for treating GBC.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Gallbladder cancer (GBC) is a prevalent biliary tract malignancy with poor patient outcomes.
- Novel therapeutic strategies are crucial for improving GBC prognosis.
- Bisbenzylisoquinoline alkaloids represent a class of compounds with potential anti-cancer properties.
Purpose of the Study:
- To investigate the anti-cancer effects of fangchinoline on gallbladder cancer cells.
- To elucidate the molecular mechanisms underlying fangchinoline's action.
- To evaluate the therapeutic potential of fangchinoline in preclinical models.
Main Methods:
- In vitro studies using GBC cell lines to assess proliferation and apoptosis.
- Techniques included Hoechst staining, TUNEL assays, and flow cytometry.
- In vivo xenograft models were used to evaluate tumor growth inhibition.
Main Results:
- Fangchinoline demonstrated dose-dependent inhibition of GBC cell proliferation and clone formation.
- Fangchinoline significantly induced apoptosis in GBC cells.
- The PI3K/Akt/XIAP anti-apoptotic pathway was suppressed by fangchinoline treatment.
- Fangchinoline treatment inhibited xenograft tumor growth in vivo.
Conclusions:
- Fangchinoline exhibits significant anti-cancer activity against gallbladder cancer.
- Fangchinoline induces apoptosis through the inhibition of the PI3K/Akt/XIAP pathway.
- Fangchinoline shows potential as a novel therapeutic agent for GBC treatment.
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