Jie Li1, Lu Hu2, Tao Zhou2, Xia Gong3, Rong Jiang4, Hongzhong Li5, Ge Kuang6, Jingyuan Wan7, Hongyuan Li8. 1. Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 2. Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. 3. Department of Anatomy, Chongqing Medical University, Chongqing 400016, China. 4. Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. 5. Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 6. Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: kuangge72@aliyun.com. 7. Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: jywan@cqmu.edu.cn. 8. Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: hongy_li@hotmail.com.
Abstract
AIM: To investigate the effects and underlying mechanisms of taxifolin on proliferation, migration and invasion of highly aggressive breast cancer in vitro and in vivo. MAIN METHODS: The antineoplastic activity of taxifolin was evaluated in MDA-MB-231 and 4 T1 cells by crystal violet assay and colony formation assay. The effects of taxifolin on migration and invasion were determined by wound healing assay and Transwell assay, respectively. mRNA and protein expression of genes were assayed respectively with qRT-PCR and western blot, and the protein expression and location was also detected by immunofluorescence and immunohistochemistry. β-catenin overexpression was performed with adenovirus infection. The effects of taxifolin on growth and metastasis of breast cancer in vivo were investigated in BALB/c mice bearing 4T1 xenografts. KEY FINDINGS: We found that taxifolin had the potential to inhibit proliferation, migration and invasion of highly aggressive breast cancer cells in a dose-dependent manner. In addition, taxifolin promoted the MET process, the reversed process of EMT, as evaluated by EMT markers and EMT-transcriptional factors in breast cancer cell lines. Meanwhile, the protein and mRNA expressions of β-catenin were dose-dependently downregulated by taxifolin, and overexpression of β-catenin by adenoviruses abrogated these beneficial effects of taxifolin above-mentioned. Furthermore, within a 4T1 xenograft mouse model, taxifolin markedly inhibited the growth of primary tumors and reduced lung metastasis of breast cancer. SIGNIFICANCE: Our findings provide a theoretical foundation for the possibility of taxifolin used as a promising agent in the clinical treatment of highly aggressive breast cancer patients.
AIM: To investigate the effects and underlying mechanisms of taxifolin on proliferation, migration and invasion of highly aggressive breast cancer in vitro and in vivo. MAIN METHODS: The antineoplastic activity of taxifolin was evaluated in MDA-MB-231 and 4 T1 cells by crystal violet assay and colony formation assay. The effects of taxifolin on migration and invasion were determined by wound healing assay and Transwell assay, respectively. mRNA and protein expression of genes were assayed respectively with qRT-PCR and western blot, and the protein expression and location was also detected by immunofluorescence and immunohistochemistry. β-catenin overexpression was performed with adenovirus infection. The effects of taxifolin on growth and metastasis of breast cancer in vivo were investigated in BALB/c mice bearing 4T1 xenografts. KEY FINDINGS: We found that taxifolin had the potential to inhibit proliferation, migration and invasion of highly aggressive breast cancer cells in a dose-dependent manner. In addition, taxifolin promoted the MET process, the reversed process of EMT, as evaluated by EMT markers and EMT-transcriptional factors in breast cancer cell lines. Meanwhile, the protein and mRNA expressions of β-catenin were dose-dependently downregulated by taxifolin, and overexpression of β-catenin by adenoviruses abrogated these beneficial effects of taxifolin above-mentioned. Furthermore, within a 4T1 xenograft mouse model, taxifolin markedly inhibited the growth of primary tumors and reduced lung metastasis of breast cancer. SIGNIFICANCE: Our findings provide a theoretical foundation for the possibility of taxifolin used as a promising agent in the clinical treatment of highly aggressive breast cancerpatients.