Luteolin inhibits angiogenesis and enhances radiotherapy sensitivity of laryngeal cancer via downregulating Integrin β1

Abstract

Aim: To demonstrate the role and mechanism of luteolin in radio-sensitization and angiogenesis of laryngeal cancer.

Methods: Firstly, we analyzed the cytotoxicity of Luteolin and radiation sensitive cytotoxicity through CCK8, and selected subsequent radiation doses and Luteolin concentrations. Next, we further analyzed the effects of Luteolin on radiation sensitivity and neovascularization of laryngeal cancer, and conducted CCK8, plate cloning, and angiogenesis experiments, respectively. At the same time, the effects of individual treatment and combination treatment on the expression of Integrin β1 and VEGFA were analyzed through immunofluorescence analysis. We also analyzed the regulation of Integrin β1 protein expression by Luteolin through Western blot. To investigate the mechanism of Integrin β1, we transfected overexpressed and silenced Integrin β1 vectors and analyzed the role of Integrin β1 in Luteolin enhancing radiation sensitivity of laryngeal cancer by repeating the above experiments. We have also constructed an in vivo subcutaneous tumor transplantation model to further validate the cell experimental results. The expression of Integrin, KI67, VEGFA, and CD31 was analyzed through Western blot and immunohistochemistry experiments.

Results: Radiation inhibited cell proliferation and decreased Integrin β1 expression, and increased the radiosensitivity through inhibiting cell proliferation, and inhibit angiogenesis during radiation. Overexpression of Integrin β1 weakened radiotherapy sensitivity on the basis of cells treated with combined administration. Integrin β1 is considered as the downstream molecule of luteolin, participating in radiosensitivity of luteolin to FaDu cells. Animal experiments also demonstrated that luteolin strengthened tumor suppression and anti-angiogenesis during radiation via Integrin β1.

Conclusion: In summary, our results manifested that radio-sensitivity effect of luteolin depended on downregulating Integrin β1 in laryngocarcinoma.

Keywords: Angiogenesis; Integrin β1; Laryngeal cancer; Luteolin; Radio-sensitization.