Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells
Abstract
:1. Introduction
2. Results and Discussion
2.1. Ophiobolin-O Reversed ADM Resistance
2.1.1. Ophiobolin-O Appeared to Reverse ADM Resistance in MCF-7/ADR Cells
2.1.2. Nuclear Morphology Changes
2.1.3. Changes of Cell Count
2.1.4. Combination with Ophiobolin-O Caused G2/M Phase Arrest in MCF-7/ADR Cells
2.1.5. Ophiobolin-O Increased the Apoptosis Rate Induced by ADM in MCF-7/ADR Cells
2.2. ROS Mediated Ophiobolin-O Sensitized G2/M Arrest and Apoptosis of MCF-7/ADR Cells
2.2.1. The Combination Effect of Ophiobolin-O on Apoptotic and Cell Cycle Proteins in MCF-7/ADR Cells
2.2.2. The Effects of Combination with Ophiobolin-O on Mitochondrial Membrane Potential of MCF-7/ADR Cells
2.2.3. ROS Was Involved in Reversal Effect of Ophiobolin-O
2.3. Ophiobolin-O Decreased the Expression of MDR1 and ADM Accumulation via Inhibiting the Activity of the MDR1 Gene Promoter
2.3.1. Ophiobolin-O Down-Regulated MDR1
2.3.2. Ophiobolin-O Inhibited Effect of P-Glycoprotein Function in MCF-7/ADR Cells
2.3.3. Ophiobolin-O Inhibited the Activity of MDR1 Gene Promoter
2.4. Inhibitory Effects on Tumor Growth of Combined Treatment with Ophiobolin-O and ADM in Nude Mice
2.5. Discussion
3. Experimental Section
3.1. Compound and Cell Culture
3.2. Cell Viability Assay
3.3. Apoptosis and Cell Cycle Assay
3.4. Real-Time PCR
3.5. Western Blotting Analysis
3.6. Rhodamine 123 (Rh123) Efflux Studies
3.7. Intracellular Adriamycin Accumulation
3.8. MDR1 Promoter Activity by Vector Transient Transfection and Dual Luciferase Assay
3.9. Mouse Xenograft Model
4. Conclusions
Acknowledgments
References
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Sun, W.; Lv, C.; Zhu, T.; Yang, X.; Wei, S.; Sun, J.; Hong, K.; Zhu, W.; Huang, C. Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells. Mar. Drugs 2013, 11, 4570-4584. https://doi.org/10.3390/md11114570
Sun W, Lv C, Zhu T, Yang X, Wei S, Sun J, Hong K, Zhu W, Huang C. Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells. Marine Drugs. 2013; 11(11):4570-4584. https://doi.org/10.3390/md11114570
Chicago/Turabian StyleSun, Wenxia, Cuiting Lv, Tonghan Zhu, Xue Yang, Shanjian Wei, Jieyin Sun, Kui Hong, Weiming Zhu, and Caiguo Huang. 2013. "Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells" Marine Drugs 11, no. 11: 4570-4584. https://doi.org/10.3390/md11114570