Investigation of Antitumor Effects of Sorafenib and Lapatinib Alone and in Combination on MCF-7 Breast Cancer Cells


Background: Breast cancer evolution and tumor progression are controlled by complex interactions betweensteroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augmentor suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigateantitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materialsand
Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5and 6.25μM concentrations of sorafenib and 200, 100, 50 and 25μM concentrations of lapatinib were administeredalone and in combination. Results were evaluated as absorbance at 450nM and IC50 values are calculated accordingto the absorbance data
Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effectson MCF-7 cells. Sorafenib exerted cytotoxic effects with an IC50 value of 32.0μM; in contrast with lapatinib theIC50 was 136.6μM. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at itsineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination showstrong anticancer effects and killed approximately 70 percent of breast cancer cells.
Conclusions: Combinationsof tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for manytypes of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatmentof breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment ofbreast cancer.