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Archive > Volume 30 Issue 3 > 2023,30(3):217-222. DOI:10.3872/j.issn.1007-385X.2023.03.005 Prev Next
Basic Research
Effect of oridonin in reversing cisplatin resistance in melanoma cells and its mechanism
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Abstract:
Objective: To investigate the effect of oridonin (Ori) in reversing cisplatin (DDP) resistance in human melanoma cells and its related mechanism. Methods: Melanoma cisplatin-resistant cell lines A375/DDP and M14/DDP were divided into control group,2 μmol/L Ori group, 4 mg/L DDP group and 2 μmol/L Ori+4 mg/L DDP group. Cell viability, invasion and migration, and apoptosis were detected by CCK-8, Annexin Ⅴ-FITC/PI staining flow cytometry and Transwell assay, respectively. The autophagosomes were observed by transmission electron microscopy, microtubule associated protein1 light chain 3 (LC3)-point structure was observed by immunofluorescence staining, and the expressions of autophagy related proteins Beclin-1, p62, LC3Ⅱ and LC3Ⅰ of A375/DDP cells were detected by WB.Results: Compared with 4 mg/LDDP group, cell proliferation viability, migration and invasion ability of 2 μmol/L Ori+4 mg/L DDP group were significantly decreased (all P<0.01), and apoptosis level was significantly increased (P<0.01). A large number of autophagosomes and LC3-point structures were observed in 4 mg/LDDPgroup; however, only a fewwere observed in 2 μmol/L Ori+4 mg/L DDP group. Compared with control group, the protein expression levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ in 4 mg/L DDP group were significantly increased (all P<0.01), but the protein expression level of p62 was significantly decreased (P<0.05 or P<0.01); compared with 4 mg/L DDP group, the protein expression levels of Beclin-1 and LC3Ⅱ/LC3Ⅰin 2 μmol/L Ori+4 mg/L DDP group were significantly decreased (all P<0.01), but the protein expression level of p62 was significantly increased (P<0.05). Conclusion: Ori can increase the sensitivity of drug-resistant melanoma cells to DDP, which may be related to the inhibition of DDP-induced autophagy.
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