Tanshinone II A improves the chemosensitivity of breast cancer cells to doxorubicin by inhibiting β-catenin nuclear translocation.

Numerous evidence link aberrant nuclear β-catenin accumulation to the development of breast cancer resistance, therefore, targeted inhibition of β-catenin nuclear translocation may effectively improve the chemosensitivity of breast cancer. Doxorubicin (Dox) is the most commonly used chemotherapeutic drug for breast cancer. Here, we determined that tanshinone II A (Tan II A) could improve the sensitivity of Dox-resistant breast cancer MCF-7/dox cells to Dox, and evaluated whether the sensitization effect of Tan II A on Dox was targeted to inhibit β-catenin nuclear translocation. The results showed that Tan II A not only significantly inhibited the nuclear translocation of β-catenin in MCF-7/dox cells treated by Dox but also inhibited the nuclear translocation of β-catenin in MCF-7 cells treated by Dox to a certain degree. Furthermore, when the above two cells treated by Dox combined with Tan II A were intervened with β-catenin agonist WAY-262611, with the re-nuclear translocation of β-catenin in the cells, the sensitization effect of Tan II A on Dox was greatly reduced. These results indicated that Tan II A could improve the chemosensitivity of breast cancer cells to Dox by inhibiting β-catenin nuclear translocation. Therefore, Tan II A could be used as a potential chemosensitizer in combination with Dox for breast cancer chemotherapy.