Metformin Sensitizes Tamoxifen Anti-Tumor Efficacy against Breast Cancer through Downregulation of c-Myc
Xu Jianxin, Guan Chen, Fang Xuejiao, Long Luye, Wang Sixuan, Qian Shihan, Lü Jianxin*
Breast cancer is a common and highly malignant tumor, finding efficient therapy to inhibit tumor growth is particularly important in clinical patient management. Tamoxifen is currently used for the treatment of estrogen receptor positive breast cancer. Metformin, the anti-diabetic drug, has been reported to reduce human cancer incidence and improves the survival of breast cancer patients. We investigated if the combination of metformin with tamoxifen could exert synergistic efficacy on breast caner cells and the underlying mechanisms. CCK-8 and plate colony formation assays were used to detect cell viability and proliferation. The flow cytometry was conducted to detect apoptosis. Cell migration assay and cell invasion assays were utilized to measure the ability of metastasis. Proteins of MAPK signaling pathway and c-Myc were detected by Western blot. The result showed that combined treatment of tamoxifen with metformin showed greater inhibition on proliferation, colony formation, migration and invasion as well as promotion of apoptosis of breast caner cells than either agent treatment alone. It showed that metformin could enhance the inhibitory effect of tamoxifen on tumor growth and downregulation of c-Myc protein demonstrated by Western blot. In conclusion, our results demonstrate that metformin enhances tamoxifen anti-tumor efficacy of breast caner cells. These effects are mediated through down-regulation of c-Myc protein. These findings may have potential clinical applications for breast caner treatment.
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