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Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation

ZHILI ZHUO#, DONGNI ZHANG#, WENPING LU*, XIAOQING WU, YONGJIA CUI, WEIXUAN ZHANG, MENGFAN ZHANG

Department of Oncology, China Academy of Chinese Medical Sciences Guang’anmen Hospital, Beijing, China

* Corresponding Author: WENPING LU. Email: email

(This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)

Oncology Research 2024, 32(6), 1093-1107. https://doi.org/10.32604/or.2024.047257

Abstract

Breast cancer is the leading cause of cancer-related deaths in women worldwide, with Hormone Receptor (HR)+ being the predominant subtype. Tamoxifen (TAM) serves as the primary treatment for HR+ breast cancer. However, drug resistance often leads to recurrence, underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates. Artemisinin (ART) has demonstrated efficacy in inhibiting the growth of drug-resistant cells, positioning art as a viable option for counteracting endocrine resistance. This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation. Five characterized genes (ar, cdkn1a, erbb2, esr1, hsp90aa1) and seven drug-disease crossover genes (cyp2e1, rorc, mapk10, glp1r, egfr, pgr, mgll) were identified using WGCNA crossover analysis. Subsequent functional enrichment analyses were conducted. Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and -sensitized patients. scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells, suggesting artemisinin’s specific impact on tumor cells in estrogen receptor (ER)-positive BC tissues. Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes. These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

Graphical Abstract

Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation

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Cite This Article

APA Style
ZHUO, Z., ZHANG, D., LU, W., WU, X., CUI, Y. et al. (2024). Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation. Oncology Research, 32(6), 1093-1107. https://doi.org/10.32604/or.2024.047257
Vancouver Style
ZHUO Z, ZHANG D, LU W, WU X, CUI Y, ZHANG W, et al. Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation. Oncol Res. 2024;32(6):1093-1107 https://doi.org/10.32604/or.2024.047257
IEEE Style
Z. ZHUO et al., "Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation," Oncol. Res., vol. 32, no. 6, pp. 1093-1107. 2024. https://doi.org/10.32604/or.2024.047257



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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