Combination treatment of bicalutamide and curcumin has a strong therapeutic effect on androgen receptor-positive triple-negative breast cancers
Triple-negative breast cancers account for approximately 15–20% of breast cancer patients. Due to lack of expression of estrogen receptor, PR and human epidermal growth factor receptor 2 in triple-negative breast cancers, there are no targeted therapies available for these cancers. Therefore, a major research priority is to find potential therapeutic targets.
Androgen receptor is present in 80–90% of all breast cancers, including 55% of estrogen receptor-α–negative cancers and 12%–35% of triple-negative breast cancers. Androgen receptor stimulates growth and survival in triple-negative breast cancer cells. Treatment with bicalutamide, an androgen receptor antagonist, has a good benefit for AR+ triple-negative breast cancer patients.
AR+ triple-negative breast cancer cells were treated with curcumin or bicalutamide alone or in a combination of both together. Cell growth, apoptosis and Wnt signaling pathways were examined. We found that curcumin dramatically suppressed Wnt signaling pathway in AR+ triple-negative breast cancer cells.
Curcumin treatment inhibited androgen receptor protein expression in AR+ triple-negative breast cancer cells. Combination treatment of curcumin and bicalutamide has a robust increase in apoptosis. Furthermore, the combination treatment suppressed the growth of AR+ triple-negative breast cancer cells more effectively than with the single drug alone.
Our data indicate that androgen receptor inhibition is a potential therapeutic approach for AR+ triple-negative breast cancers. In summary, our study for the first time shows that the combination treatment of curcumin and bicalutamide is effective in AR+ triple-negative breast cancer cells.