In this study, we confirmed that hypoxia is an important feature of osteosarcoma, validated by the positive immunohistochemistry staining of hypoxia marker hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CAIX) in osteosarcoma tissue samples.
Here, we quantified protein level of HIF-1α in human osteosarcoma U2OS cells treated with ascochlorin-related compounds and typical HIF-1α stabilizers to characterize properties of HIF-1α stabilization by 4-<i>O</i>-methylascochlorin.
We found that hBMSC-MVs promoted U2OS cell proliferation and migration under hypoxia in vitro, and that was partially associated with the PI3K/AKT and HIF-1α pathways.
The purpose of the present study was to investigate the role and underlying mechanism of SUMO-specific protease 1 (SENP1)/hypoxia-inducible factor-1α (HIF-1α) feedback loop in hypoxic microenvironment of OS.
In this paper, the therapeutic mechanism of R rosea for AMS was investigated by analysis of the relationship between R rosea compositions and hypoxia-inducible factor 1 (HIF-1) degradation pathway.System biology and network biology, computational approaches were used to explore the molecular mechanisms of traditional Chinese medicine (TCM).Our results showed that chemical compositions of R rosea could inhibit the targets of HIF-1 degradation pathway in multi-composition/multi-target ways.We conclude that the 18 components with more than 2 targets and 5 targets (arrest-defective-1 [ARD1], forkhead transcription factor [FOXO4], osteosarcoma-9 [OS-9], prolyl hydroxylase 2 [PHD2], human double minute 2 [Hdm2]) deserve to be noticed, and PHD2, receptor for activated C-kinase1 (RACK1) and spermidine/spermine-N1-acetyltransferase-1 (SSAT1) may be the targets of active ingredients of rhodionin, rhodiosin, and rhodiolatuntoside, respectively.
HIF-1 was overexpressed in osteosarcoma tissues and cell lines, which promoted cell proliferation, clone formation, migration, invasion and inhibited cell apoptosis.
Taken together, our findings suggest that THC suppresses metastasis and invasion and this may be associated with HIF-1α and autophagy, which would potentially provide therapeutic strategies for human osteosarcoma.
According to these findings, miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation and migration via directly targeting HIF-1α.
The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis.
In this study, we found that the expression of HIF-1α was significantly increased, while miR-20b obviously decreased in OS patients and OS cell lines compared with healthy controls.
To investigate the effects of NDV infection on HIF-1α in cancer cells, the osteosarcoma (Saos-2), breast carcinoma (MCF-7), colon carcinoma (HCT116) and fibrosarcoma (HT1080) cell lines were used in the present study.
DEC2 knockdown in osteosarcoma cell lines (U2OS, MNNG and 143B) attenuated HIF-1α accumulation and impaired the up-regulation of HIF-1 target genes in response to hypoxia.
Although 8-week treatment led to eventual loss of HIF1α(PP) expression, treated osteosarcoma U-2 OS cells acquired tumorigenicity in the subcutaneous tissue.
Moreover, the function of HIF1 in osteosarcoma cells was further investigated in in-vitro experiments by regulating HIF1 and vascular endothelial growth factor-A (VEGF-A) expression.
We performed immunohistochemistry, immunocytochemistry, quantitative real-time PCR, Western blots and fluorescent reporter assays to evaluate the correlation between CXCR4 and HIF-1α expression in human osteosarcoma specimens or SOSP-9607 cells under normoxic and hypoxic conditions.