Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through regulating miR-520b/ATG7 axis

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Chemo-resistance presents a significant challenge in effective cancer treatment.
• Apigenin, a dietary flavonoid, exhibits anticancer properties in various malignancies.
• Hepatocellular carcinoma (HCC) often develops resistance to standard chemotherapies like doxorubicin.

Purpose of the Study:

• To investigate the chemo-sensitizing potential of apigenin in doxorubicin-resistant HCC cells.
• To elucidate the molecular mechanisms underlying apigenin's chemo-sensitizing effects.
• To evaluate apigenin's efficacy in an in vivo model of HCC.

Main Methods:

• Utilized a doxorubicin-resistant hepatocellular carcinoma cell line (BEL-7402/ADM).
• Assessed the effects of apigenin on doxorubicin sensitivity, miR-520b expression, and autophagy.
• Employed miR-520b mimics and ATG7 inhibition/targeting studies.
• Evaluated apigenin's anti-tumor activity in a xenograft mouse model.

Main Results:

• Apigenin significantly enhanced doxorubicin sensitivity in BEL-7402/ADM cells.
• Apigenin treatment led to increased miR-520b expression and inhibited ATG7-dependent autophagy.
• miR-520b mimics replicated the chemo-sensitizing effect and autophagy inhibition.
• ATG7 was identified as a direct target of miR-520b.
• Apigenin suppressed tumor growth in vivo by up-regulating miR-520b and inhibiting ATG7.

Conclusions:

• Apigenin acts as a chemo-sensitizer in doxorubicin-resistant hepatocellular carcinoma.
• The miR-520b/ATG7 pathway is crucial for apigenin's chemo-sensitizing effects.
• Apigenin demonstrates potential as a therapeutic agent to overcome chemo-resistance in HCC.