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Archive > Volume 32 Issue 8 > 2025,32(8):823-830. DOI:10.3872/j.issn.1007-385X.2025.08.005 Prev Next
Basic Research
Pristimerin enhances the doxorubicin sensitivity of breast cancer MCF-7 cells via the AKT/GSK-3β signaling pathway
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Abstract:
[Abstract] Objective: To investigate the effect of pristimerin (PT) on doxorubicin (DOX) sensitivity of huamn breast cancer cell MCF-7 by regulating the protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. Methods: MCF-7 cells were cultured in vitro and used to construct a DOX resistant cell line MCF-7/DOX. MCF-7 cells were separated into the NC group, the L-PT group (2 μmol/L PT), the M-PT group (4 μmol/L PT), the H-PT group (8 μmol/L PT), the H-PT+SC79 group (8 μmol/L PT + 10 μmol/L AKT/GSK-3β signaling pathway inhibitor SC79), and the H-PT + LY294002 group (8 μmol/L PT + 2.5 μmol/L AKT/GSK-3β signaling pathway activator LY294002). MCF-7/DOX cells were separated into the MCF-7/DOX group (untreated), the DOX group (50 nμmol/L DOX), PT + DOX group (8 μmol/L PT and 50 nμmol/L DOX), the PT + DOX + SC79 group (8 μmol/L PT + 50 nμmol/L DOX + 10 μmol/L SC79), and the PT + DOX + LY294002 group (8 μmol/L PT + 50 nμmol/L DOX + 2.5 μmol/L LY294002). MTT assay, plate cloning assay, scratch assay, Transwell assay, and WB assay were applied respectively to determine cell proliferation, colony formation, migration, invasion, and AKT/GSK-3β signaling pathway protein expression in each group. Establish a MCF-7 cell xenograft model in nude mice to observe the effects of PT on tumor growth and the protein expression of the AKT/GSK-3β signaling pathway in the tumor tissues. Results: Compared with the NC group, the proliferation rate, colony formation rate, scratch healing rate, invasive cell count, and the p-AKT, p-GSK-3β protein expressions of MCF-7 cells in the L-PT group, the M-PT group, and the H-PT group all showed a PT concentration dependent decrease (all P < 0.05). Compared with the H-PT group, the trend of changes in the above indicators of MCF-7 cells in the H-PT + SC79 group was opposite to the above, while the trend of changes in the above indicators of MCF-7 cells in the PT + DOX + LY294002 group was the same (all P < 0.05). There was no significant difference in the proliferation rate, colony formation number, scratch healing rate, invasive cell count, and expressions of p-AKT and p-GSK-3β proteins between the MCF-7/DOX group and the DOX group (all P > 0.05). Compared with the MCF-7/DOX group and the DOX group, the PT + DOX group showed a decrease in the above indicators of MCF-7/DOX cells (all P < 0.05). Compared with the PT + DOX group, the above indicators in the PT + DOX + SC79 group all increased, while the above indicators in the PT + DOX + LY294002 group all decreased (all P < 0.05). Transplant tumor experiment in nude mice showed that compared with those in the control group and the DOX group, the mass and volume of transplant tumors, p-AKT and P-GSK-3β protein expressions in the PT + DOX group all decreased (all P < 0.05). Conclusion: PT can inhibit the proliferation, migration, and invasion of BC cells, and enhance their sensitivity to DOX chemotherapy., Its mechanism is related to the inhibition of the AKT/GSK-3β signaling pathway.
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