SP600125, an inhibitor of Jnk pathway, reduces viability of relatively resistant cancer cells to doxorubicin.

We identified four breast cancer cell lines and one stomach cancer cell line resistant to the cytotoxic effects of doxorubicin (DOX) and examined their sensitivity to other chemotherapeutic agents. SP600125, an inhibitor of the Jnk pathway, reduced the cellular viability of all five DOX-resistant cancer cell lines. Jnk1 siRNA also reduced the viability of the one DOX-resistant cell line in which it was tested. Similar results were produced in an in vivo mouse model, in which the volume of tumors derived from the DOX-resistant cell line was reduced more effectively by treatment with SP600125 than by treatment with DOX, whereas those from a DOX-sensitive cell line were reduced only by DOX treatment. Overall, these results may contribute to the development of chemotherapeutic treatments for patients with DOX-resistant tumors.