Icaritin enhances the efficacy of cetuximab against triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) has a greater risk of recurrence and metastasis along with a worse prognosis compared with other subtypes of breast cancer. Studies have revealed that mitogenic estrogen signaling is involved in the malignant proliferation of TNBC cells through a novel variant of the estrogen receptor, estrogen receptor alpha -36 (ER-alpha 36). The results of the present study demonstrated that knockdown of ER-alpha 36 expression in TNBC cells using short hairpin RNA inhibited rapid estrogen signaling bypass activation of the PI3K/AKT signaling pathway. Moreover, the ER-alpha 36 modulator icaritin inhibited the proliferation of TNBC cells both in vitro and in vivo. Here, it was revealed that the combination of icaritin and cetuximab, a therapeutic epidermal growth factor receptor (EGFR) neutralizing antibody, induced apoptosis and inhibited cell proliferation synergistically in TNBC cells. The results of the present study improved the understanding of the underlying mechanisms of TNBC progression and supported the therapeutic potential of combined treatment targeting the ER-alpha 36 and EGFR.