Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis
Abstract
:1. Introduction
2. Results
2.1. AR/AhR Co-Regulate ABCG2 Expression in Serous EOC
2.2. AR Reduces Sensitivity and Develops Resistance to Paclitaxel in Serous EOC
2.3. Paclitaxel Induces AR/AhR–ABCG2 Axis in Serous EOC
2.4. Degrading AR for Paclitaxel Insensitivity/Resistance Therapy in Serous EOC
3. Discussion
3.1. New Mode of AR Activation by Exposure to Paclitaxel
3.2. Novel Therapeutic Strategy by Degrading AR in EOC Tumors
4. Materials and Methods
4.1. Patient Tissue Study
4.2. Immunohistochemistry and Quantitation of Staining Score
4.3. Cell Lines and Reagents
4.4. Immunoblotting Assay
4.5. Transfection and Lentivirus Infection Procedure
4.6. Total RNA Isolation and cDNA Synthesis
4.7. Quantitative Real-Time PCR Analysis
4.8. Cell Viability Assay and IC50 Values
4.9. Colony Formation Assay and Standard Cell Number Count
4.10. ABCG2 Efflux Capacity Assay
4.11. Genomic DNA Extraction and PCR Amplification
4.12. ABCG2 Promoter Region Plasmid Construction and Luciferase Reporter Assay
4.13. Chromatin Immunoprecipitation (ChIP)
4.14. Co-Immunoprecipitation
4.15. Establishment of Paclitaxel-Resistant Ovarian Cancer Cell Line
4.16. Animal Xenograft Transplantation
4.17. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Chung, W.-M.; Ho, Y.-P.; Chang, W.-C.; Dai, Y.-C.; Chen, L.; Hung, Y.-C.; Ma, W.-L. Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis. Cancers 2019, 11, 463. https://doi.org/10.3390/cancers11040463
Chung W-M, Ho Y-P, Chang W-C, Dai Y-C, Chen L, Hung Y-C, Ma W-L. Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis. Cancers. 2019; 11(4):463. https://doi.org/10.3390/cancers11040463
Chicago/Turabian StyleChung, Wei-Min, Yen-Ping Ho, Wei-Chun Chang, Yuan-Chang Dai, Lumin Chen, Yao-Ching Hung, and Wen-Lung Ma. 2019. "Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis" Cancers 11, no. 4: 463. https://doi.org/10.3390/cancers11040463