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To explore the potential mechanism of nobiletin in improving the sensitivity of breast cancer MDA-MB-231 cells to Pirarubicin. MDA-MB-231 cells were randomly divided into Control group, Nobiletin group, Pirarubicin group and Nobiletin co-Pirarubicin group. CCK-8 assay was used to detect the inhibitory effect of Nobiletin co-Pirarubicin on the proliferation of MDA-MB-231 cells, and the cell cycle and apoptosis of MDA-MB-231 cells were detected by flow cytometry. The effect of nobiletin combined with Pirarubicin on the migration and repair ability of MDA-MB-231 cells was detected by scratch test. Western blotting was used to determine the effect of nobiletin co-Pirarubicin on Period2 (PER2), apoptosis-related proteins Bax and BCL-2 expression levels in MDA-MB-231 cells. The results showed that the sensitivity of MDA-MB-231 cells to Pirarubicin was enhanced by nobiletin. Compared with Pirarubicin or nobiletin alone, Pirarubicin combined with nobiletin promoted the apoptosis of MDA-MB-231 cells and the expression of apoptosis-related protein Bax, and reduced the expression of apoptosis-inhibiting protein BCL-2. The combination of nobiletin and Pirarubicin significantly inhibited the proliferation and promoted the apoptosis of MDA-MB-231 cells, which may be mediated by the enhancement of PER2 expression by nobiletin.

Nobiletin enhances Pirarubicin chemosensitivity of breast cancer cell MDA-MB-231 by regulating PER2