Glioma angiogenesis is boosted by ELK3 activating the HIF-1[Formula: see text]/VEGF-A signaling axis.

BACKGROUND: Clinical studies have shown that first-line use of anti-angiogenetic therapy can prolong progression-free survival but little progress has been made in extending the overall survival of the patients. We explored the role of ELK3 in glioma angiogenesis to improve and design more efficacious therapies. METHODS: A tissue microarray and immunohistochemistry analysis were used to determine the expression of ELK3 protein in 400 glioma patients. Cell proliferation, metastasis, cell cycle, and apoptosis were monitored in U87 and U251 cells using CCK-8, EdU, transwell assays, and flow cytometry. A tube-formation assay, a rat aorta ring sprouting assay, and a matrigel plug assay were performed to examine the antiangiogenic activity of ELK3. An ELISA, Western blot, and correlation analysis of the CGGA dataset were used to detect the association between ELK3 and VEGF-A or ELK3 and HIF-1[Formula: see text]. Besides, orthotopic transplantation in nude mice and histopathological and immunological analysis of in vitro tumors were used to explore the effect of ELK3 on tumor progression and median survival. RESULTS: ELK3 was upregulated in glioma tissues and associated with a poor prognosis. In vitro, ELK3 promoted cell proliferation and cell cycle progression, induced metastasis, and suppressed apoptosis. Then, silencing ELK3 inhibited VEGF-A expression and secretion by facilitating HIF-1[Formula: see text] degradation via ubiquitination. Finally, knockdown ELK3 inhibited tumor progression and angiogenesis in vitro and in vivo, as well as prolonged nude mice's median survival. CONCLUSIONS: Our findings first evidenced that ELK3 is crucial for glioma because it promotes angiogenesis by activating the HIF-1[Formula: see text]/VEGF-A signaling axis. Therefore, we suggest that ELK3 is a prognostic marker with a great potential for glioma angiogenesis and ELK3-targeted therapeutic strategies might hold promise in improving the efficacy of anti-angiogenic therapies.

Establishment of Fluorescence Sensitization Method for Hydroxysafflor Yellow A.

As the main active ingredient in Chinese medicine safflower, hydroxysafflor yellow A (HSYA) has multiple pharmacological effects. In the work, the absorption and fluorescence spectra of HSYA under different environmental conditions (such as acidity, temperature, ions, viscosity, and surfactant) were investigated. The fluorescence intensity of HSYA varied greatly with acidity, temperature, viscosity, and surfactant, but was less affected by common cations and anions. Among various surfactants, we found that borax can significantly enhance the HSYA fluorescence intensity, and thus, a borax-HSYA sensitization system for HSYA fluorescence was established. In the optimized sensitization system, the fluorescence intensity of HSYA increased by 20 times and showed a good linearity with HSYA concentrations in the range of 0∼10 µM with a detection limit of 8 nM. The borax-HSYA sensitization system is nontoxic to T24 cells and mice and can be used for the fluorescence imaging of HSYA in cells, thereby providing an effective method for analyzing HSYA in vitro and monitoring its metabolism in cells.