Effects of zoledronic acid on the expression of HIF-1α and VEGF in the osteosarcoma cell line LM8 under hypoxic condition
- Author:
- No author available
- Journal Title:
- JOURNAL OF CHINESE PHYSICIAN
- Issue:
- 9
- DOI:
- 10.3760/cma.j.issn.1008-1372.2009.09.004
- Key Word:
- 二膦酸盐类/药理学;骨肉瘤/药物疗法/代谢;细胞低氧/药物作用;DNA结合蛋白质类/代谢;血管内皮生长因子类/代谢;Diphosphonates/PD;Osteosarcoma/DT/ME;Cell hypoxia/DE;DNA-binding proteins/ME;Vascular endothelial growth factors/ME
Abstract： Objective To investigate the effects of zoledronic acid on the expression of HIF-1α and VEGF in osteosarcoma LM8 cell line under hypoxic condition. Methods The hypoxic culture model was established. After LM8 cells were treated with zoledronic acid, semi-quantitative PCR was used to assess the expression of HIF-1α and VEGF mRNA. The expression of HIF-lct and VEGF protein was de-tected by immunohistochemical staining and ELISA respectively. Results Compared with cells in normoxic conditions, cells in the hypoxic environment and cells treated with zoledronic acid in the hypoxic condition did not show a significant change in the mRNA level of HIF-1α(P >0. 05). However, the protein expression of HIF-1α was markedly decreased in the cells treated with zoledronic acid in the hypoxic envi-ronment. In contrast, both mRNA and protein expression levels of VEGF were down-regulated in the zoledronic acid treatment hypoxic group (P <0.05). Conclusion Under hypoxic conditions in vitro, zoledronic acid inhibited the expression of HIF-1α protein, which decreased VEGF mRNA level and protein expression in osteosarcorna LM8 cell line.
- [1]Rogers MJ,Coxon FP.The role of prenylated small GTP-binding proteins in the regulation of osteoclast function.[J].2003,72(1).
- [2]Gregg L, Semenza.Targeting HIF-1 for cancer therapy.[J].2003,3(10).
- [3]Tenta R,Kletsas D,Alexis MN,etc.Mechanisms of the Action of Zoledronic Acid on Human MG-63 Osteosarcoma Cells.[J].2008,40(11).
- [4]Horie N,Koto K,Maekawa T,etc.Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model.[J].2009,274(2).
- [5]Oh SH,Han JY,Hong WK,etc.Hypoxia-inducible factor 1alpha and antiangiogenic activity of farnesyltransferase inhibitor SCH66336 in human aerodigestive tract cancer.[J].2005,97(17).
- [6]Spugnini EP,Vincenzi B,Caruso G,etc.Zoledronic acid for the treatment of appendicular osteosarcoma in a dog[J].2009,50(1).
- [7]G A, Rodan,T J, Martin.Therapeutic approaches to bone diseases.[J].2000,289(5484).
- [8]Kyu-Sil Choi,Moon-Kyoung Bae,Joo-Won Jeong,etc.Hypoxia-induced Angiogenesis during Carcinogenesis[J].2003,36(1).
- [9]Maxwell PH,Astuti D,Hooper L,etc.The pVHL-associated SCF ubiquitin ligase complex: molecular genetic analysis of elongin B and C, Rbx1 and HIF-1alpha in renal cell carcinoma.[J].2001,20(36).
- [10]Poellinger L,Fujii Kuriyama-Y,Sogawa K,etc.Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300.[J].1999,18(7).
- [11]H, Zhong,F, Agani,A A, Baccala,etc.Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer.[J].1998,58.