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已发表论文
基于孟德尔随机化和实验研究识别西黄丸治疗乳腺癌的潜在治疗靶点
Authors Tang Y , Yang Z , Ye Z, Su H, Zhu R , Meng X, Zheng Q
Received 9 October 2025
Accepted for publication 28 January 2026
Published 6 February 2026 Volume 2026:18 572244
DOI https://doi.org/10.2147/BCTT.S572244
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Professor Robert Clarke
Yuning Tang,1 Zhuotao Yang,1 Zhihao Ye,2 Haotian Su,3 Ruotong Zhu,4 Xuli Meng,2,* Qinghui Zheng2,*
1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 4The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xuli Meng, Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email mxlmail@126.com Qinghui Zheng, Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email zhengqinghui@hmc.edu.cn
Purpose: Breast cancer remains a major threat to women’s health worldwide, with drug resistance posing a significant challenge to treatment efficacy. Xihuang Pill (XHP), a traditional Chinese medicine formula, has demonstrated anti-tumor potential in breast cancer. However, its complex composition makes elucidating its precise molecular mechanisms difficult. This study aimed to identify key targets and mechanisms of XHP against breast cancer by integrating network pharmacology with Mendelian randomization analyses based on large-scale genome-wide association study (GWAS) and expression quantitative trait loci (eQTL) datasets, and thereby overcoming the subjectivity and uncertainty inherent in traditional target prediction.
Methods: Active ingredients and targets of XHP were retrieved from TCMSP and SymMap databases. Breast cancer risk-related genes were identified using summary-data-based MR (SMR) analysis integrating blood eQTL data from eQTLGen and GWAS data from FinnGen. Overlapping targets between XHP and breast cancer were analyzed. In vitro experiments, including siRNA knockdown and treatment with XHP-containing serum, were conducted on MCF-7 and MDA-MB-231 breast cancer cells to assess the roles of identified targets on cell proliferation (CCK-8 assay) and migration (wound healing assay), and to verify XHP’s effects on target expression (Western blot, qRT-PCR).
Results: Network pharmacology identified 383 potential XHP targets. SMR analysis revealed 33 genes significantly associated with breast cancer risk. Intersection analysis pinpointed GSTM1 and SLC22A5 as overlapping targets. Notably, GSTM1 is a key enzyme involved in glutathione metabolism and cellular detoxification, whereas SLC22A5 (OCTN2) is a crucial transporter responsible for carnitine uptake and cellular energy metabolism. MR analysis indicated that higher expression of both genes was associated with reduced breast cancer risk. In vitro, silencing GSTM1 or SLC22A5 promoted proliferation and migration of breast cancer cells. Conversely, XHP-containing serum upregulated GSTM1 and SLC22A5 expression and significantly inhibited cancer cell proliferation and migration.
Conclusion: XHP may inhibit breast cancer cell proliferation and migration by upregulating GSTM1 and SLC22A5, offering new insights for precision TCM therapy.
Keywords: breast cancer, Xihuang pill, Mendelian randomization, GSTM1, SLC22A5
1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 4The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xuli Meng, Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email mxlmail@126.com Qinghui Zheng, Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email zhengqinghui@hmc.edu.cn
Purpose: Breast cancer remains a major threat to women’s health worldwide, with drug resistance posing a significant challenge to treatment efficacy. Xihuang Pill (XHP), a traditional Chinese medicine formula, has demonstrated anti-tumor potential in breast cancer. However, its complex composition makes elucidating its precise molecular mechanisms difficult. This study aimed to identify key targets and mechanisms of XHP against breast cancer by integrating network pharmacology with Mendelian randomization analyses based on large-scale genome-wide association study (GWAS) and expression quantitative trait loci (eQTL) datasets, and thereby overcoming the subjectivity and uncertainty inherent in traditional target prediction.
Methods: Active ingredients and targets of XHP were retrieved from TCMSP and SymMap databases. Breast cancer risk-related genes were identified using summary-data-based MR (SMR) analysis integrating blood eQTL data from eQTLGen and GWAS data from FinnGen. Overlapping targets between XHP and breast cancer were analyzed. In vitro experiments, including siRNA knockdown and treatment with XHP-containing serum, were conducted on MCF-7 and MDA-MB-231 breast cancer cells to assess the roles of identified targets on cell proliferation (CCK-8 assay) and migration (wound healing assay), and to verify XHP’s effects on target expression (Western blot, qRT-PCR).
Results: Network pharmacology identified 383 potential XHP targets. SMR analysis revealed 33 genes significantly associated with breast cancer risk. Intersection analysis pinpointed GSTM1 and SLC22A5 as overlapping targets. Notably, GSTM1 is a key enzyme involved in glutathione metabolism and cellular detoxification, whereas SLC22A5 (OCTN2) is a crucial transporter responsible for carnitine uptake and cellular energy metabolism. MR analysis indicated that higher expression of both genes was associated with reduced breast cancer risk. In vitro, silencing GSTM1 or SLC22A5 promoted proliferation and migration of breast cancer cells. Conversely, XHP-containing serum upregulated GSTM1 and SLC22A5 expression and significantly inhibited cancer cell proliferation and migration.
Conclusion: XHP may inhibit breast cancer cell proliferation and migration by upregulating GSTM1 and SLC22A5, offering new insights for precision TCM therapy.
Keywords: breast cancer, Xihuang pill, Mendelian randomization, GSTM1, SLC22A5