For example, SIRT1 causes tamoxifen resistance in ER-α-positive BC cells through upregulation of multidrug resistance protein 2 by mediating deacetylation of FoxO1 protein.412 Subsequently, SIRT1 inhibition impairs nuclear FoxO1 and multidrug resistance protein 2 expression and augments the cytotoxic effect of paclitaxel and doxorubicin in tamoxifen-resistant BC cells.412 SIRT3 overexpression in BC cell line MTR-3 reduces the sensitivity of the resistant cells to tamoxifen.357,413 On the contrary, SIRT4 enhances the tamoxifen sensitivity of BC cells via inhibiting the STAT3 signaling pathway. Here, STAT3 is linked to breast cancer.