Knockdown of ROS1 gene sensitizes breast tumor growth to doxorubicin in a syngeneic mouse model.

Knockdown of ROS1 gene sensitizes breast tumor growth to doxorubicin in a syngeneic mouse model.
Int J Oncol. 2016 Mar 23;
Authors: Tiash S, Chua MJ, Chowdhury EH
Abstract
Treatment of breast cancer, the second leading cause of female deaths worldwide, with classical drugs is often accompanied by treatment failure and relapse of disease condition. Development of chemoresistance and drug toxicity compels compromising the drug concentration below the threshold level with the consequence of therapeutic inefficacy. Moreover, amplification and over-activation of proto-oncogenes in tumor cells make the treatment more challenging. The oncogene, ROS1 which is highly expressed in diverse types of cancers including breast carcinoma, functions as a survival protein aiding cancer progression. Thus we speculated that selective silencing of ROS1 gene by carrier-mediated delivery of siRNA might sensitize the cancer cells to the classical drugs at a relatively low concentration. In this investigation we showed that intracellular delivery of c-ROS1-targeting siRNA using pH-sensitive inorganic nanoparticles of carbonate apatite sensitizes mouse breast cancer cells (4T1) to doxorubicin, but not to cisplatin or paclitaxel, with the highest enhancement in chemosensitivity obtained at 40 nM of the drug concentration. Although intravenous administrations of ROS1-loaded nanoparticles reduced growth of the tumor, a further substantial effect on growth retar...

Source: International Journal of Oncology - March 22, 2016 Category: Cancer & Oncology Authors: Tiash S, Chua MJ, Chowdhury EH Tags: Int J Oncol Source Type: research