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Archive > Volume 25 Issue 7 > 2018,25(7):716-720. DOI:10.3872/j.issn.1007-385X.2018.07.010 Prev Next
Basic Research
Role of FOXO3a in hypoxia-induced cisplatin resistance in osteosarcoma U-2OS cells
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Abstract:
Objective:To investigate the role of FOXO3a in hypoxia-induced cisplatin (DDP) resistance in osteosarcoma cells. Methods:The FOXO3a expression was detected by RT-PCR and Western blotting in osteosarcoma U-2OS cell line under normoxia and hypoxia conditions. The effects of HIF-1α-siRNA and FOXO3a-siRNA on the expressions of HIF-1αand FOXO3a were detected by Western blotting. CCK-8 and Annexin V/PI assays were used to detect the function of FOXO3a in hypoxia-induced DDP resistance of U-20S cells. Results: Hypoxia could significantly increase the mRNA and protein levels of FOXO3a in U-2OS cells (All P<0.05). The expression of FOXO3a was regulated by HIF-1α; compared with control group and HIF-1α -NC group, the FOX03a protein expression was significantly down-regulated in HIF-1α-siRNA group [(0.38±0.03) vs (0.89±0.08)，(0.91±0.07), all P<0.01]. Under hypoxia condition,FOXO3a-siRNA could decrease the tolerance of U-2OS cells to DDP [(38.50±2.83)% vs (61.75±5.73)%, P<0.01], and increase DDP-induced apoptosis of U-2OS cells [(73.41±6.13)% vs (32.38±2.23)%, (55.89±4.46)%, All P<0.05]. Conclusions: Hypoxia significantly enhanced DDP-resistance of U-2OS cells by increasing FOXO3a expression in a HIF-1-dependent manner.
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