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Avicenna Journal of Phytomedicine، جلد ۱۵، شماره ۵، صفحات ۱۵۴۶-۱۵۶۱
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عنوان انگلیسی Synergistic inhibitory effects of Trifolium pratense L. extract and doxorubicin on 4T1 tumor-bearing mice are mediated via targeting the Wnt/β-catenin pathway and reversal of epithelial-mesenchymal transition
چکیده انگلیسی مقاله Objective: Triple-negative breast cancer (TNBC) presents significant therapeutic challenges. This study investigates the combination effects of Trifolium pratense L. (red clover) and doxorubicin (DOX) on the Wnt/β-catenin signaling pathway, epithelial-mesenchymal transition (EMT) and apoptosis in 4T1 tumor-bearing BALB/c mice.Materials and Methods: Female BALB/c mice were divided into six (n=10) groups: control, DOX (5 mg/kg), and three treatment groups receiving 100, 200, or 400 mg/kg T. pratense extract alongside DOX, and a single dose of 400 mg/kg T. pratense. Tumor size was measured using Vernier calipers, and survival rates were analyzed through Kaplan-Meier curves.  Tumors were removed to analyze histological examinations and gene expression of Ccnd, Myc, Cdh1, Snai1, Sfrp2, Wif1, Kremen1, and ARHGAP17. Immunohistochemical staining was performed to evaluate p53, Ki-67, β-catenin, Cdh1, and vimentin expression.Results: Co-treatment of T. pratense (400 mg/kg) with DOX (5 mg/kg) synergistically reduced cell proliferation and increased apoptosis by increasing p53 and decreasing Ki-67 expression in a dose-dependent manner. This co-treatment effectively inhibited the Wnt/β-catenin pathway by upregulating antagonists (Wif1 and Sfrp2), modulating β-catenin accumulation, and reversing EMT through increased E-cadherin expression and decreased vimentin (protein level) and Snai1 (gene expression) levels.Conclusion: T. pratense extract shows potential as an adjuvant therapy against TNBC by targeting the Wnt/β-catenin pathway and reversing EMT while enhancing DOX efficacy. Further research is warranted to explore additional anticancer mechanisms of T. pratense extract.
کلیدواژه‌های انگلیسی مقاله Trifolium pratense L. Doxorubicin Epithelial, mesenchymal transition Wnt signaling pathway beta catenin
نویسندگان مقاله | Saeed khazayel
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.


| Mohammad Hossein Faraji
Physiology Division, Department of Basic Science, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.


| mohsen akbari bazm
Department of Anatomical Sciences, Kermanshah University of Medical Sciences


| Mozafar khazaei
Fertility and Infertility Research Center, Health Technology Institute School of Medicine, University Ave., Shahid Shiroudi Blvd, Kermanshah, Iran


| Elham Niromand
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.


| Mohammad Rasool khazaei
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
نشانی اینترنتی https://ajp.mums.ac.ir/article_25940.html
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نوع مقاله منتشر شده Original Research Article
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