Antiproliferative effects of anastrozole on MCF-7 human breast cancer cells in vitro are significantly enhanced by combined treatment with testosterone undecanoate.
The present study aimed to assess the effects of aromatase inhibitor anastrozole and testosterone undecanoate, separately and in combination, on proliferation and apoptosis in MCF-7 human breast cancer cells cultured in vitro. The effects of various concentrations of these drugs on the proliferation of MCF-7 cells were evaluated by CCK8 assay, the levels of cell apoptosis were evaluated by flow cytometry with Annexin-V/propidium iodide staining and androgen receptor (AR) protein expression was determined by western blot analysis. The results of the CCK8 assay indicated that greater antiproliferative activity was detected in the MCF-7 cells in the combined treatment groups, compared with those treated with anastrozole or testosterone undecanoate alone. Flow cytometric analysis of apoptosis revealed that treatment with a combination of the two drugs generated a higher percentage of apoptotic cells, particularly when the two drugs were applied for 48 h, compared with single drug treatment. Western blot analysis revealed a significant decrease in AR protein expression in the combined treatment groups compared with MCF7 cells treated with single drugs. The results of the present study provided evidence supporting the potential of a combination of anastrozole and testosterone undecanoate as a novel therapeutic strategy for the treatment of breast cancer. Furthermore, it was demonstrated that the antiproliferative effects of anastrozole were significantly enhanced by combined treatment with testosterone undecanoate via the AR signaling pathway.
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Rong
R
Chen
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Junwei
J
Cui
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Qinqin
Q
Wang
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Peng
P
Li
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Xiaoling
X
Liu
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Hui
H
Hu
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Wei
W
Wei
D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D009570:Nitriles / Q000008:administration & dosage*; D011944:Receptors, Androgen / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014230:Triazoles / Q000008:administration & dosage*
D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D011944:Receptors, Androgen; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone; C010792:testosterone undecanoate