Carbonate apatite-facilitated intracellular delivery of c-ROS1 small interfering RNA sensitises MCF-7 breast cancer cells to cisplatin and paclitaxel

in the presence of anti-cancer drugs to MCF-7 cells whereas the 3-(4, 5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide assay and Western blot were performed to assess the cell viability and detect the phosphorylation levels of mitogenactivated protein kinase and AKT1, respectively. Results Intracellular delivery of the siRNA targeting c-ROS1 gene transcript in MCF cells which constitutively express the gene, dose-dependently enhanced chemosensitivity to cisplain and paclitaxel, while demonstrating no significant enhancement in cell death with doxorubicin irrespective of its doses following intracellular delivery of the siRNAs. Discussion pH-sensitive carbonate apatite has recently been developed as an efficient device to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with siRNA, the desirable size distribution of the resulting siRNA-apatite complex for effective cellular endocytosis and the ability of the internalised siRNA to escape the endosomes resulting in the effective knockdown of the target gene, such as cyclin B1 or ABCB1 transporter gene. The synergistic effect of c-ROS1 siRNA and paclitaxel on cell death as reported in this paper could be correlated with the inhibition of ERK 1/2 phosphorylation in mitogen- activated protein kinasepathway. Conclusion Thus, ROS1 has evolved as a potential target for gene knockdown in cisplatin- and paclitaxel-based chemotherapy of human breast cancer.