Anti-angiogenesis by Volatile Oil of Citrus medica var. sarcodactylis from Hejiang on U87 Cells through the VEGF/VEGFR Signaling Pathway
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Abstract:
To study the in vitro antitumor activity of the volatile oil of Citrus medica var. sarcodactylis from Hejiang and its anti-angiogenic effects on the transplanted human glioma cells U87 in nude mice, a CCK-8 assay was used to screen tumor cells sensitive to the volatile oil in vitro. Tumor models were established by transplanting the U87 cells to nude mice to observe the effects of volatile oil (at 12.5, 25, and 50 mg/kg) on the tumor growth, microvessel density (MVD), expressions of vascular endothelial growth factors (VEGF), and expressions of the receptors VEGFRs (flt-1 and KDR) of the transplanted U87 cells in vivo. As the IC50 values of the volatile oil on four tumor cell lines, namely U87, MCF-7, A549, and HepG2 are 82.19 μg/mL, 173.99 μg/mL 215.83 μg/mL, and 192.87 μg/mL, respectively, U87 cells are the most sensitive to the oil. After the oral administration of the volatile oil, the tumor volume (TV), relative TV, and relative tumor proliferation ratio decrease significantly; therefore, the volatile oil can significantly inhibit the growth of transplanted tumors in nude mice. The microvessel distribution of the volatile oil-treated group is sparse compared to that of the control. Meanwhile, the MVD value decreases from 63.24 (control) to 30.65, 46.88, 40.18, and 36.56, whereas the relative expression of VEGF decreases from 0.93 to 0.19, 0.52, 0.33, and 0.16. The relative expression of flt-1 reduces from 0.82 to 0.18, 0.50, 0.32, and 0.09, whereas that of KDR reduces from 0.78 to 0.14, 0.48, 0.30, and 0.11. In short, the volatile oil exhibit significant in vitro antitumor activity, with its effects on U87 cells being the most evident. The in vivo antiglioma effects may be realized via the VEGF/VEGFR signaling pathway to achieve antiangiogenesis in tumors.
