Abstract
Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and 6.25μM concentrations of sorafenib and 200, 100, 50 and 25μM concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and IC50 values are calculated according to the absorbance data Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an IC50 value of 32.0μM; in contrast with lapatinib the IC50 was 136.6μM. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.
Highlights
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women
The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer
When partially When partially effective concentration of sorafenib (S 25μM) combined with partially effective concentration of lapatinib (L 100μM) which killed %41.74 of MCF cells, it has been observed that cytotoxic effect of combination was statistically significantly higher when compared to both sorafenib and lapatinib alone (p
Summary
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. ER functions as a ligand dependent transcription factor and promotes variety of genes Many of these gene products directly promote breast cancer cell proliferation, survival and tumor progression (Arpino et al, 2008; Osborne and Schiff, 2005). Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. We aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Results were evaluated as absorbance at 450nM and IC50 values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. A combination of these two agents may be a promising therapeutic option in treatment of breast cancer
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