Wang et al., 2019 - Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1. Journal of experimental & clinical cancer research : CR   38:371 Full text @ J. Exp. Clin. Cancer Res.

Fig. 2

20-HETE or PGE2 partly reverses the antiangiogenic activities of the screened molecules in the zebrafish embryo. a The zebrafish embryos in 96-well microplate were treated with the indicated concentrations of compounds [isoliquiritigenin (ISL), glabridin (GLA) and hesperetin (HSP), 10 μM] alone, the compounds (10 μM) plus 20-HETE or PGE2, and vehicle for 48 h. Selected images of angiogenesis in the zebrafish embryo in different groups as shown in (a); Average vessel length for each group (b). The values are presented as the mean ± SEM, n = 20. *P < 0.05; **P < 0.01 vs. control; #P < 0.05; ##P < 0.01 vs. ISL, GLA or HSP-treated groups

Fig. 3

20-HETE or PGE2 partly reverses the antiangiogenic activities of isoliquiritigenin (ISL) in the rabbit cornea. A 7–0 black silk was used to pass the rabbit corneal stroma 1 mm from the horizontal to the limbus with a length of 3 mm to induce corneal neovascularization model. One week after suturing, the suture was removed, and the flavonoid ISL (1 and 2 mg/ml), ISL (2 mg/ml) plus 20-HETE or PGE2, and vehicle were performed twice a day for a week in eye drops. Photographs were taken with a stereomicroscope at day 0, 3 and 7 after treatment (a), and the vessel areas were quantified using image pro plus 6.0 (b). The values are presented as the mean ± SEM, n = 6. *P < 0.05; **P < 0.01 vs. control; #P < 0.05; ##P < 0.01 vs. ISL or GLA-treated groups

Fig. 4

Isoliquiritigenin (ISL) prolongs survival, delays growth and induces vessel normalization in C6 gliomas with the decreased intratumoral level of 20-HETE and PGE2a In the C6 intracranial glioma model, the survival time of the rats (n = 10) injected intraperitoneally with ISL (10 and 20 mg/kg), Sunitinib (80 mg/kg) or vehicle was measured, and 20-HETE and PGE2 in the tumor tissues from each group were determined at day 12 by LC-MS/MS or ELISA. b In the C6 subcutaneous glioma model, rat C6 glioma cells (5 × 106) were injected subcutaneously into the right flank of Wistar rats. When tumors reached a size of about 100 mm3, the rats (n = 8) received ISL (10 and 20 mg/kg), Sunitinib (80 mg/kg) or vehicle by intraperitoneal injection once daily for a week. Tumor weight was measured, and 20-HETE and PGE2 were determined by LC-MS/MS or ELISA. The values are presented as the mean ± SEM, *P < 0.05, **P < 0.01 vs. control, #P < 0.05, ##P < 0.01 vs. sunitinib (80 mg/kg)-treated group. c-h Rat C6 glioma cells (5 × 106) were injected subcutaneously into the right flank of Wistar rats. When tumors reached a size of about 100 mm3, the rats (n = 8) received ISL (10 and 20 mg/kg) or vehicle by intraperitoneal injection once daily for a week. Tumor perfusion at day 0, 2, 4, 6 and 8 was measured using a laser Doppler analyzer. Scale bars, 2 mm (c). The quantitative analysis showed the relative level of tumor perfusion (d). After sacrificing the rats at day 8, hypoxia induced factor (HIF)-1α in the tumor tissues was measured by Western blot (e). Double staining for CD31 (green) and α-SMA (red) in the tumor tissues was shown. Scale bars, 50 μm (f-h). i In the C6 intracranial glioma model, the survival time of the rats (n = 10) injected intraperitoneally with ISL (20 mg/kg), temozolomide (TMZ, 20 mg/kg), ISL (20 mg/kg) plus TMZ (20 mg/kg) or vehicle was measured, and TMZ uptake into tumor tissues was determined at day 12 by high performance liquid chromatography (HPLC). j In another experiment, rat C6 glioma cells (5 × 106) were injected subcutaneously into the right flank of Wistar rats. When tumors reached a size of about 100 mm3, the rats (n = 8) received ISL (20 mg/kg), TMZ (20 mg/kg), ISL (20 mg/kg) plus TMZ (20 mg/kg) or vehicle by intraperitoneal injection once daily for a week. Tumor weight was measured, and TMZ uptake into tumor tissues was determined by HPLC. The values are presented as the mean ± SEM, *P < 0.05, **P < 0.01 vs. control, #P < 0.05, ##P < 0.01 vs. TMZ (20 mg/kg)-treated group

Acknowledgments:
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ J. Exp. Clin. Cancer Res.