Comparison of the efficacy of carboplatin, oxaliplatin and cisplatin, with various concentrations of epidermal growth factor family ligands, in killing human triple-negative breast cancer cells

Abstract

Current breast cancer therapies focus on the use of hormones to control tumor cells. However, triple negative breast cancers (TNBC) lack receptors for the hormones estrogen and progesterone, in addition to the HER-2 protein. As such, TNBC therapy is often limited to non-targeted chemotherapeutic agents. Another receptor present on the cell surface of most TNBC cells is epidermal growth factor receptor (EGFR), which could serve as a target for new therapies. EGFR drives cell proliferation following its activation by epidermal growth factor (EGF) family ligands. These ligands include amphiregulin, betacellulin, and EGF, which were chosen for use in this study. Little research has been done on the use of EGF family ligands in combination with established cancer therapies. EGF has been shown to have an effect on the rate of cancer cell death when combined with platinum-based DNA alkylating agents in head and neck cancers. In this combination therapy, the conflicting messages from the stimulating ligand and the alkylating agent cause an enhanced rate of cell death apparently by more targeted and efficient drug delivery to the cell nucleus. We have hypothesized that EGF family ligands can be combined with alkylating agents for synergistic killing of EGFR-expressing TNBC cells. The tests of hypothesis described here were pharmacological dose-response studies. Our results show that different EGF family ligands have markedly different effects on EGF receptor trafficking and subsequent cell death when combined with platinum drugs. To extend our results beyond breast cancer cells, the treatments also were compared in another EGFR-expressing cancer model, brain glioblastoma.NIHNo embarg