Novel multi-kinase inhibitor, T03 inhibits Taxol-resistant breast cancer

Activation of kinase-associated signaling pathways is one of the leading causes of various malignant phenotypes in breast tumors. Strategies of drug discovery and development have investigated approaches to target the inhibition of protein kinase signaling. In the current study, the anti-tumor activities of a novel multi-kinase inhibitor, T03 were evaluated in breast cancer. T03 inhibited Taxol-resistant breast cancer cell proliferation and induced cell cycle arrest and apoptosis in vitro and in vivo. The current results demonstrated that T03 downregulated c-Raf, platelet-derived growth factor receptor-β and other kinases, thus inhibited Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and Akt/mechanistic target of rapamycin survival pathways in MCF-7 and MCF-7/Taxol xenograft tumors. At a dose of 100 mg/kg, T03 inhibited tumor growth by 62.90 and 59.98% in tumor weight in MX-1 and MX-1/T xenograft models, respectively and by 62.60 and 60.22% in MCF-7 and MCF-7/T tumors, respectively. These data indicate that the novel multi-kinase inhibitor, T03, may present as a potential compound to develop novel treatments against breast cancer and Taxol-resistant breast tumors.