Effect of dexmedetomidine on proliferation, migration and invasion ability of renal carcinoma cells and relationship with ferroptosis / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of dexmedetomidine (Dex) on the proliferation, migration and invasion ability of renal carcinoma cells and the relationship with ferroptosis.Methods:Experiment Ⅰ GRC-1 cells at the logarithmic growth phase were selected and divided into 5 groups ( n=6 each) using a random number table method: control group (group C) and different concentrations of dexmedetomidine groups(D1, D2, D3, and D4 groups). Group C was routinely incubated for 24 h. D1, D2, D3, and D4 groups were incubated with dexmedetomidine at 0.1, 1.0, 10.0 and 100.0 μmol/L respectively, for 24 h. The cell proliferation ability was assessed by CCK-8 assay.The cell migration and invasion ability was was evaluated by Transwell chamber assay. Experiment Ⅱ GRC-1 cells at the logarithmic growth phasewere selected and divided into 3 groups ( n=6 each) using a random number table method: control group (group C), dexmedetomidine group (group D), and dexmedetomidine+ Ferrostatin-1 group (group D+ F). Group C was routinely cultured for 24 h. Dexmedetomidine 10 μmol/L was added and cells were incubated for 24 h in group D. Dexmedetomidine 10 μmol/L was added, Ferrostatin-1 1 μmol/L was simultaneously added, and then cells were incubated for 24 h in group D+ F. The proliferation ability of the cells was tested by CCK-8 assay, and the migration and invasion ability of the cells was detected by Transwell assay. The contents of glutathione (GSH), malondialdehyde (MDA) and Fe 2+ were measured by the colorimetric method. The expression of glutathione peroxidase 4(GPX4) and ATF4-induced solute carrier family 7a member 11 (SLC7A11) was detected by Western blot. Results:Experiment I Compared with group C, the cell proliferation and the number of migrating and invading cells were significantly decreased in D3 and D4 groups ( P<0.05), and no significant change was found in aforementioned indexes in D1 and D2 groups ( P>0.05). Experiment Ⅱ Compared with group C, the cell proliferation and the number of migrating and invading cells were significantly decreased, the content of Fe 2+ was increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated ( P<0.05), and no significant change was found in MDA content in group D( P>0.05). Compared with group D, the cell proliferation and the number of migrating and invading cells were significantly increased, the content of Fe 2+ was decreased, the content of GSH was increased, the expression of GPX4 and SLC7A11 was up-regulated ( P<0.05), and no significant change was found in the MDA content in group D+ F( P>0.05). Conclusions:Dexmedetomidine can inhibit the proliferation, migration and invision ability of renal carcinoma cells, and the mechanism is related to promotion of ferroptosis.