Zhongnan Hospital of Wuhan University, Department of Orthopedics, Wuhan University, Wuhan, Hubei 430071, P.R. China.
Oncol Rep. 2017 Jul;38(1):336-342. doi: 10.3892/or.2017.5655. Epub 2017 May 22.
Recently, hypoxia inducible factor-1 (HIF-1) was reported to be correlated with isocitrate dehydrogenase 1 (IDH-1) in several types of tumors. However, the expression and significance of HIF-1 and IDH-1 in osteosarcoma is still unknown. In the present study, the expression levels of IDH-1 and HIF-1α in 35 formalin-fixed paraffin-embedded sections from osteosarcoma patients were investigated by immunohistochemistry. The expression levels of IDH-1 and HIF-1α in human osteosarcoma cell lines (MG-63 and 143B) were further detected by western blotting under normal and hypoxic conditions. In addition, HIF-1α was downregulated via lentiviral vector‑mediated RNA interference (RNAi) in the MG-63 human osteosarcoma cell line. The results revealed that HIF-1α was negatively correlated with IDH-1 in the osteosarcoma tissues. Both in MG-63 and 143B cell lines, the expression of HIF-1α was increased while IDH-1 was decreased under a hypoxic condition compared to normal conditions. HIF-1α downregulation promoted IDH-1 expression in the MG-63 cell line under either normal or hypoxic conditions. In conclusion, our findings suggest that HIF-1α inhibits IDH-1 in osteosarcoma and consequently increases the incidence of osteosarcoma.
最近，有报道称缺氧诱导因子-1（HIF-1）与几种类型肿瘤中的异柠檬酸脱氢酶 1（IDH-1）相关。然而，HIF-1 和 IDH-1 在骨肉瘤中的表达和意义尚不清楚。在本研究中，通过免疫组织化学法检测了 35 例骨肉瘤患者福尔马林固定石蜡包埋切片中 IDH-1 和 HIF-1α的表达水平。在正常和缺氧条件下，通过 Western blot 进一步检测了人骨肉瘤细胞系（MG-63 和 143B）中 IDH-1 和 HIF-1α的表达水平。此外，通过慢病毒载体介导的 RNA 干扰（RNAi）下调了 MG-63 人骨肉瘤细胞系中的 HIF-1α。结果表明，HIF-1α与骨肉瘤组织中的 IDH-1 呈负相关。与正常条件相比，在 MG-63 和 143B 细胞系中，缺氧条件下 HIF-1α 的表达增加，而 IDH-1 的表达减少。在正常或缺氧条件下，HIF-1α 的下调促进了 MG-63 细胞系中 IDH-1 的表达。综上所述，我们的研究结果表明，HIF-1α 在骨肉瘤中抑制 IDH-1，从而增加骨肉瘤的发生率。
