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| Effect of Urolithin A on Malignant Biological Behavior of Triple-Negative Breast Cancer Cells via AKT/mTOR Signaling Pathway |
| A Jigu, HAN Jizhen, CHEN Yanyan, et al |
| Cancer Hospital, Xinjiang Medical University, Xinjiang Urumqi 830011, China |
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Abstract Objective: To investigate the effect of urolithin A (UA) on the malignant biological behavior of triple-negative breast cancer (TNBC) cells and its regulatory mechanism on the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.Methods: The safety and toxicity of UA were assessed on human normal breast epithelial cell line MCF-10A and TNBC cell line MDA-MB-231 using the CCK-8 assay. MDA-MB-231 cells were randomly divided into the following groups: MDA-MB-231, MDA-MB-231 + UA, MDA-MB-231 + AKT activator (SC79), and MDA-MB-231 + UA + AKT activator (UA + SC79). The proliferation activity of each group was detected by colony formation assay. Cell migration and invasion abilities were examined by wound healing and Transwell assays. Apoptosis was assessed by flow cytometry. The activation levels of AKT/mTOR signaling pathway-related proteins were detected by Western blot.Results: UA at a concentration of 7.5μmoL/L was determined to be safe for normal breast cells and toxic to breast cancer cells. Compared to the MDA-MB-231 group, the UA group showed decreased colony formation (105.67±9.18), cell migration rate (12.92±2.13), invasion cell count (56.33±3.68), and p-AKT/AKT (0.12±0.02) and p-mTOR/mTOR (0.16±0.03) levels (P<0.05), while the apoptosis rate (22.1±1.75) increased (P<0.05). In contrast, the SC79 group showed increased colony formation (222±17.57), cell migration rate (62.7±6.14), invasion cell count (233.33±15.43), and p-AKT/AKT (0.58±0.07) and p-mTOR/mTOR (0.74±0.08) levels (P<0.05), and decreased apoptosis rate (4.57±0.57) (P<0.05). The addition of SC79 reversed the inhibitory effects of UA on the malignant biological behavior of MDA-MB-231 cells (P<0.05).Conclusion: UA can inhibit the proliferation, migration, invasion, and anti-apoptotic activities of TNBC cells by suppressing the AKT/mTOR signaling pathway.
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2024, Vol. 30 
