Resveratrol Contrasts LPA-Induced Ovarian Cancer Cell Migration and Platinum Resistance by Rescuing Hedgehog-Mediated Autophagy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Reagents
2.3. Antibodies
2.4. Wound-Healing Migration Assay
2.5. Transwell In Vitro Cell Migration Assay
2.6. One Color Microarray Genome-Wide Gene Expression Analysis
2.7. Bioinformatic Analysis
2.8. Western Blot Analysis
2.9. Immunofluorescence
2.10. 3D Spheroids Forming Assay
2.11. Assessment of Autophagy in Living Cells Expressing GFP-LC3
2.12. Gene Silencing
2.13. Imaging Acquisition and Analysis
2.14. Statistical Analysis
3. Results
3.1. Resveratrol Counteracts LPA-Induced Ovarian Cancer Cell Migration
3.2. Resveratrol and LPA Oppositely Modulate the Transcriptomic of Ovarian Cancer Cells and Particularly the Genes of the Hedgehog Pathway and Epithelial-to-Mesenchymal Transition
3.3. Resveratrol Reverses LPA-Induced EMT along with Restoration of Autophagy
3.4. LPA Stimulates While Resveratrol Inhibits the Hedgehog-Mediated EMT
3.5. BMI-1 Silencing Restores Autophagy and Prevents LPA-Induced EMT
3.6. Ovarian Cancer Patients with Low Expression of Hedgehog/EMT Markers along with Upregulated Autophagy Have a Better Prognosis
3.7. Resveratrol and Hedgehog Inhibitors Rescue Cell Growth Control and Responsiveness to Platinum
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Ferraresi, A.; Esposito, A.; Girone, C.; Vallino, L.; Salwa, A.; Ghezzi, I.; Thongchot, S.; Vidoni, C.; Dhanasekaran, D.N.; Isidoro, C. Resveratrol Contrasts LPA-Induced Ovarian Cancer Cell Migration and Platinum Resistance by Rescuing Hedgehog-Mediated Autophagy. Cells 2021, 10, 3213. https://doi.org/10.3390/cells10113213
Ferraresi A, Esposito A, Girone C, Vallino L, Salwa A, Ghezzi I, Thongchot S, Vidoni C, Dhanasekaran DN, Isidoro C. Resveratrol Contrasts LPA-Induced Ovarian Cancer Cell Migration and Platinum Resistance by Rescuing Hedgehog-Mediated Autophagy. Cells. 2021; 10(11):3213. https://doi.org/10.3390/cells10113213
Chicago/Turabian StyleFerraresi, Alessandra, Andrea Esposito, Carlo Girone, Letizia Vallino, Amreen Salwa, Ian Ghezzi, Suyanee Thongchot, Chiara Vidoni, Danny N. Dhanasekaran, and Ciro Isidoro. 2021. "Resveratrol Contrasts LPA-Induced Ovarian Cancer Cell Migration and Platinum Resistance by Rescuing Hedgehog-Mediated Autophagy" Cells 10, no. 11: 3213. https://doi.org/10.3390/cells10113213