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[Grape seed proanthocyanidins extract inhibits pancreatic cancer cell growth through down-regulation of miR-27a
Jia Ma1, Binbin Fang, Fanpeng Zeng
1Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu Anhui 233030, China.
Objective:
To explore the eff ect of grape seed proanthocyanidins extract (GSPE) on the growth of pancreatic cancer cells and the underlying mechanisms.
Methods:
The pancreatic cancer AsPC-1 cells were cultured in vitro. The effects of GSPE on cell proliferation, apoptosis and migration were analyzed by MTT, Annexin V-FITC/PI and Transwell migration assay, respectively. The expression of miR-27a and FOXO1 in AsPC-1 cells was determined by real-time RT-PCR and Western blot, respectively. The miR-27a inhibitors were applied to verify the role of miR-27a in mediation of GSPE effects.
Results:
GSPE inhibited cell growth in a dose-dependent manner. This inhibitory effect was significant when the dosage of GSPE was more than 50 μg/mL (P<0.05 vs control). GSPE also could induce apoptosis and inhibit cell migration. MiR-27a expression was notably down-regulated when the dosage of GSPE was 75 μg/mL (P<0.01 vs control). Compared with the control group, cell proliferation inhibition was significantly increased in the miR-27a inhibitor group, the GSPE group and the miR-27a inhibitor plus GSPE group (P<0.01), while cell migration was significantly decreased (P<0.01). Compared with the GSPE or the miR-27a inhibitor group, the growth and migration inhibitory effects in the miR-27a inhibitor plus GSPE group were more obviously (P<0.01). Both GSPE and miR-27a inhibitor alone could up-regulate FOXO1 expression. But these effects were more apparent when they are applied in combination.
Conclusion:
GSPE inhibites AsPC-1 cells' growth and migration partly through down-regulation of miR-27a expression.
Insights
Grape seed proanthocyanidins extract (GSPE) inhibits pancreatic cancer cell growth and migration. This effect is partly mediated by down-regulating miR-27a expression and up-regulating FOXO1.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Pancreatic cancer remains a significant health challenge with limited effective treatments.
- Grape seed proanthocyanidins extract (GSPE) is a natural compound with potential anti-cancer properties.
- Understanding the molecular mechanisms of GSPE action is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the inhibitory effects of GSPE on pancreatic cancer cell growth.
- To elucidate the underlying molecular mechanisms, focusing on miR-27a and FOXO1.
- To assess the impact of GSPE on cell proliferation, apoptosis, and migration.
Main Methods:
- In vitro culture of AsPC-1 pancreatic cancer cells.
- Assessment of cell proliferation, apoptosis, and migration using MTT, Annexin V-FITC/PI, and Transwell assays.
- Quantification of miR-27a and FOXO1 expression via real-time RT-PCR and Western blot.
- Validation of miR-27a's role using miR-27a inhibitors.
Main Results:
- GSPE demonstrated dose-dependent inhibition of pancreatic cancer cell growth, significantly above 50 μg/mL.
- GSPE induced apoptosis and suppressed cell migration.
- GSPE significantly down-regulated miR-27a expression and up-regulated FOXO1 expression.
- Combined GSPE and miR-27a inhibitor treatment showed enhanced inhibition of growth and migration.
Conclusions:
- GSPE exhibits anti-proliferative and anti-migratory effects on AsPC-1 pancreatic cancer cells.
- The observed effects are partly attributed to the down-regulation of miR-27a and up-regulation of FOXO1.
- GSPE represents a potential therapeutic agent for pancreatic cancer, warranting further investigation.
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