Abstract
Breast cancer is one of the leading fatal diseases for women worldwide who cannot have surgery typically have to rely on systemic chemotherapy to extend their survival. Doxorubicin (DOX) is one of the most commonly used chemotherapeutic agents against breast cancer, but acquired resistance to DOX can seriously impede the efficacy of chemotherapy, leading to poor prognosis and recurrences of cancer. Resveratrol (RES) is a phytoalexin with pharmacological antitumor properties, but its underlying mechanisms are not clearly understood in the treatment of DOX‐resistant breast cancer. We used cell viability assays, cell scratch tests, and transwell assays combined with Western blotting and immunofluorescent staining to evaluate the effects of RES on chemoresistance and the epithelial‐mesenchymal transitions (EMTs) in adriamycin‐resistant MCF7/ADR breast cancer cells, and to investigate its underlying mechanisms. The results showed that a treatment of RES combining with DOX effectively inhibited cell growth, suppressed cell migration, and promoted cell apoptosis. RES reversed EMT properties of MCF7/ADR cells by modulating the connection between SIRT1 and β‐catenin, which provides a hopeful therapeutic avenue to conquer DOX‐resistance and thereby prolong survival rates in breast cancer patients.
Highlights
The incidence of breast cancer has increased rapidly in recent years, making it become the most common malignancy in females worldwide with about 278,000 new cases and 64,000 deaths in 2013.1 The occurrence of breast cancer is usually associated with endocrine factors, genetic mutation, procreation, and precancerous lesions
We demonstrated for the first time that RES reversed DOX‐resistance, inhibited migration capacity of breast cancer DOX‐resistant cells by modulating epithelial‐mesenchymal transitions (EMTs) phenotype and SIRT1/β‐catenin pathway
We showed a new mechanism that underlies the progression of β‐catenin, and suggested that the molecular principle of RES may be used in DOX‐resistance in breast cancer
Summary
The incidence of breast cancer has increased rapidly in recent years, making it become the most common malignancy in females worldwide with about 278,000 new cases and 64,000 deaths in 2013.1 The occurrence of breast cancer is usually associated with endocrine factors, genetic mutation, procreation, and precancerous lesions. Chemoresistance to DOX can impede the therapeutic effect, Xiaoxia Jin and Yingze Wei are contributed to this study Whether RES takes effect on the DOX‐resistance and metastasis of breast cancer cells remains to be further studied, and the transformation of EMT in this process should be investigated as well. RES successfully alleviated cell migration and increased synergistic sensitivity to DOX through reducing EMT processes and regulating the correlation between silent mating type information regulation 2 homologue 1 (SIRT1) and β‐catenin. Our work suggests new avenues for use of RES as a potential effective adjuvant drug in breast cancer treatment to overcome DOX‐resistance as well as tumor metastasis. Further investigation of the potential mechanisms for RES use with DOX and in prospective clinical trials is warranted
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