AUTHOR=Li Huayao , Gao Chundi , Liang Qing , Liu Cun , Liu Lijuan , Zhuang Jing , Yang Jing , Zhou Chao , Feng Fubin , Sun Changgang TITLE=Cryptotanshinone Is a Intervention for ER-Positive Breast Cancer: An Integrated Approach to the Study of Natural Product Intervention Mechanisms JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.592109 DOI=10.3389/fphar.2020.592109 ISSN=1663-9812 ABSTRACT=

Background: Resistance to endocrine therapy has hampered clinical treatment in patients with ER-positive breast cancer (BRCA). Studies have confirmed that cryptotanshinone (CPT) has cytotoxic effects on BRCA cells and can significantly inhibit the proliferation and metastasis of ER-positive cancer cells.

Methods: We analyzed the gene high-throughput data of ER-positive and negative BRCA to screen out key gene targets for ER-positive BRCA. Finally, the effects of CPT on BRCA cells (MCF-7 and MDA-MB-231) were examined, and quantitative RT-PCR was used to evaluate the expression of the key targets during CPT intervention.

Results: A total of 169 differentially expressed genes were identified, and revealed that CPT affects the ER-positive BRCA cells by regulating CDK1, CCNA2, and ESR1. The overall experimental results initially show that MCF-7 cells were more sensitive to CPT than MDA-MB-231 cells, and the expression of ESR1 was not affected in the BRCA cells during CPT intervention, while the expression of CDK1 and CCNA2 were significantly down-regulated.

Conclusion: CPT can inhibit the proliferation and migration of BRCA cells by regulating CDK1, CCNA2, and ESR1, especially in ER-positive BRCA samples. On the one hand, our research has discovered the possible mechanism that CPT can better interfere with ER+ BRCA; on the other hand, the combination of high-throughput data analysis and network pharmacology provides valuable information for identifying the mechanism of drug intervention in the disease.