Биологическое и клиническое значение 7-гидроксиматаирезинола: от теории к практике

Abstract

Among all the properties of 7-hydroxymatairesinol (7-HMR), the least studied are antitumor ones, including against the background of fibrocystic mastopathy (FCM). Objective. To study the effects of 7-HMR on the growth rate of the tumor node in outbred female mice with a standard model of spontaneous breast cancer (BC; Ehrlich carcinoma, EC), as well as the effect of oral administration of 7-HMR on the balance of estrogen metabolites and their ratios, lipid profile and some clinical aspects of the course of FCM. Materials and methods. Experiment: Ehrlich carcinoma (EC) model with growth stimulation with estradiol valerate (EV, 0.51 mg/kg, female mice (n = 90), 5 groups (n = 18): (1) EC, 7-HMR, 60 mg/ kg/day, i.g., (2) EC, 7-GMR, 120 mg/kg/day, i.g., (3) EC, 7-GMR at a dose of 120 mg/kg per day + EV, i.g., (4) CE + EV, i.g., 21 days, (5) control, CE, no drugs. Results. Administration of EVs led to a slight increase in the growth rate of tumor nodes, which was statistically significantly inhibited by taking 7-HMR (120 mg/kg/day) on day 21: the average volume of a tumor node was 321.9 mm3, (p = 0.007), (control with EV). Sixty women were observed: patients with FCM (~52.6 years) and participants without FCM (n = 20, ~55 years). Estrogen derivatives and their ratios in urine per day were measured: 16a-ONE1, 2-ONE2, 2-ONE1, 4-OMEE2, 2-OMEE1, 4-ONE1, 2-ONE1/16a-ONE1, 2-ONE1/2-OMeE1 and 4-OHE1/4-OMeE1. Hyperestrogenism was detected in patients with FCM. The use of 7-HMR (60 mg/day, 30 days) decreased the content of estradiol (at baseline – 15.10 ± 4.8 μg/day; after taking 7-HMR – 1.63 ± 0.2 μg/day; p < 0.05), estrone (at baseline – 13.99 ± 3.02 mcg/day; after taking 7-GMR. – 2.42 ± 0.03 mcg/day, p < 0.05) in the FCM group. The use of 7-HMR reduced the concentration of 16a-ONE1 in patients with FCM by -1.80 μg/day, p = 0.03. During treatment, an increase in the ratio of 2-ONE1/16a-ONE1 metabolites was detected in the FCM group (at baseline – 1.69 ± 0.09 μg/day, after 7-HMR – 3.7 ± 0.48 μg/day, trend, p = 0.09). In general, in 67.5% of patients with FCM, positive dynamics of therapy were established, including elimination of the pain syndrome of FCM. Key words: Lignans, 7-hydroxymatairesinol, Ehrlich's solid carcinoma, mice, estrogens, combination therapy, fibrocystic breast disease