Noscapine Inhibiting the Growth and Angiogenesis of Human Eutopic Endometrium of Endometriosis Patients through Expression of Apoptotic Genes and Nitric Oxide Reduction in Three-Dimensional Culture Model

Abstract

Noscapine is a natural alkaloid with anti-angiogenesis activities. The aim of the present study was to examine the effect of noscapine on eutopic endometrium of endometriosis patients (EEE) and normal endometrium (NE)in a three-dimensional (3D) culture model. In this experimental in-vitro study, EEE (n = 8) and NE (n = 8) biopsies were taken from 16 reproductive aged women. The biopsies were cleared from blood and mucus. Each biopsy was cut into small fragments (1 Í 1 mm) in a sterile condition. For 3D culture, the endometrial fragments were put between two layers of fibrin jell made of fibrinogen solution [3 mg/mL in Medium199 (M199) + thrombin]. Twenty-four wells of culture dish was divided into 5 groups for each biopsy: the control wells were treated with M199 containing 5% fetal bovine serum (FBS) while, the test wells were exposed to the same media containing one of the noscapine doses (10, 50, 100, and 200 μM). The expression of apoptotic genes, growth score, angiogenesis, and nitric oxide (NO) secretion were evaluated. The mean of growth score of groups exposed to 0, 10, 50, 100, and 200 μM were 2.2 ± 0.55, 1.7 ± 0.45, 1.44 ± 0.27, 0.29 ± 0.1, and 0.1 ± 0.08 in EEE, and also, 2.11 ± 0.6, 1.65 ± 0.5, 0.79 ± 0.41, 0.18 ± 0.1, and 0.1 ± 0.1 in NE, respectively, and the difference between the groups was significant (P < 0.05). The expression of apoptotic genes significantly increased while, the levels of Bcl-2 and Sirt1 reduced (P = 0.004). NO secretion reduced significantly (P < 0.05) in both EEE and NE groups. In conclusion, higher doses of noscapine showed inhibitory effect on growth and angiogenesis of EEE and NE.