XBP1 gene silencing augments quercetin-induced apoptosis and anti-metastatic activity in breast cancer cell lines

Abstract This study investigated the combined effects of quercetin (Que) and shRNA-mediated XBP1 silencing on the MCF7 and MDA-MB-231 breast cancer cell lines. Que was selected because of its well-known anticancer effects. XBP1, on the other hand, was targeted because it has been reported to play a critical role in the progression of breast cancer and in stress-adaptive signaling. Cell viability and colony formation assays showed that Que and XBP1 silencing reduced cell growth, with the combined treatment producing a more pronounced inhibitory effect. In both cell lines, the combined treatment was associated with increased expression of apoptosis-related markers, including CASP3, CASP8 and CASP9, supporting a pro-apoptotic response. In addition, treatment-related changes were observed in EMT-associated markers, including increased CDH1 expression and decreased CDH2 expression, suggesting modulation of EMT-related molecular characteristics. Overall, these findings indicate that the combined application of XBP1 silencing and Que exerts anti-proliferative and apoptosis-associated effects on breast cancer cells and may also influence EMT-related molecular pathways. These results support the potential of combining RNAi-based approaches with plant-derived natural compounds as a therapeutic strategy for breast cancer.