Role of FOXO3a in hypoxia-induced cisplatin resistance in osteosarcoma U-2OS cells
10.3872/j.issn.1007-385x.2018.07.010
- VernacularTitle:FOXO3a在缺氧诱导骨肉瘤U-2OS细胞顺铂耐药中的作用
- Author:
ZHANG Ling
1
;
SHAO Hua
1
Author Information
1. (Department of Pharmacy, Zhongda HospitalAffiliated to Southeast University, Nanjing 21009, Jiangsu, China
- Publication Type:Journal Article
- Keywords:
forkhead box O 3a（FOXO3a）;
hypoxia；osteosarcom;
U-2OS cell;
cisplatin;
drug resistance
- From:
Chinese Journal of Cancer Biotherapy
2018;25(7):716-720
- CountryChina
- Language:Chinese
-
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-siRNAand FOXO3a-siRNAon 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 U20S cells. Results: Hypoxia could significantly increase the mRNAand 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.
- Full text:20180710.pdf
