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Archive > Volume 31 Issue 6 > 2024,31(6):579-585. DOI:10.3872/j.issn.1007-385X.2024.06.006 Prev Next
Basic Research
Triptolide inhibits the proliferation and induces ferroptosis of osteosarcoma U2OS cells via the miR-34b-5p/Notch1 axis
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Abstract:
Objective: To investigate the mechanism of triptolide (TPL) regulating Notch1 expression on ferroptosis of osteosarcoma U2OS cells via miR-34b-5p. Method: U2OS cells were routinely cultured and divided into the control group , the TPL (10 μmol/L) group, the TPL (10 μmol/L)+Fer-1 (ferroptosis inhibitor, 20 μmol/L) group, the miR-NC, miR-34b-5p, miR-34b-5p+Fer-1 (20 μmol/L) group, the TPL (10 μmol/L)+anti-miR-34b-5p group, and the anti-miR-34b-5p+Fer-1 (20 μmol/L) group. qPCR assay, CCK-8 assay, ferric ion detection reagent, DHE-fluorescent probe, and WB assay were used to detect the expression of miR-34b-5p, the proliferative ability, and the level of Fe2+, ROS levels and the expression of GPX4, SLC7A11 and Notch1 proteins, respectively. Dual luciferase reporter gene assay was used to verify the targeted binding relationship between miR-34b-5p and Notch1. Results: TPL promoted miR-34b-5p expression in U2OS cells, while Fer-1 and anti-miR-34b-5p inhibited miR-34b-5p expression (all P<0.05）. TPL significantly inhibited the proliferation of U2OS cells, the expression of ferroptosis-related proteins (GPX4, SLC7A11, and Notch1 proteins), and increased the cellular Fe2+ and ROS content, and Fer-1 reversed the effect of TPL on U2OS cells (all P<0.05）. Overexpressing miR-34b-5p had similar effects on U2OS cells as TPL (all P<0.05）. miR-34b-5p can be targeted to bind Notch1 (all P<0.05）. miR-34b-5p inhibitor could significantly inhibit the effect of TPL on U2OS cells (all P<0.05）. Fer-1 could enhance the effect of miR-34b-5p inhibitor (all P<0.05）. Conclusion: TPL inhibits the proliferative capacity and promotes ferroptosis of U2OS cells, and its mechanism may be related to the targeted regulation of Notch1 expression by miR-34a-5p.
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