Lichong decoction inhibits micro-angiogenesis by reducing the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor in hysteromyoma mouse model.

OBJECTIVE:To investigate the efficacy of Lichong decoction (LD) from Traditional Chinese Medicine, on micro-angiogenesis in a mouse model of hysteromyoma. METHODS:A mouse model of hysteromyoma was developed by orthotopic intrauterine injection of primary human myoma cells isolated from patients from the Beijing Obstetrics and Gynecology Hospital into CB-17 Scid mice. Mice were administered high-dose LD, low-dose LD, mifepristone or water (control) daily by gavage for 4 weeks. Uterine diameter and coefficient (uterine weight/body weight) were measured. Uterine morphology was assessed by light microscopy (hematoxylin and eosin) and transmission electron microscopy. Serum levels of estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone (LH) were measured by enzyme-linked immunosorbent assay. Uterine protein expression of hypoxia inducible factor (HIF)-1α, CD31 and proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. VEGF and HIF-1α mRNAs were quantified by RT-PCR. RESULTS:High-dose LD, low-dose LD and mifepristone reduced uterine diameter and coefficient, and attenuated the morphologic abnormalities associated with hysteromyoma. High-dose LD, low-dose LD and mifepristone inhibited hysteromyoma-induced micro-angiogenesis, as evidenced by a decrease in the number of new microvessels co-immunostaining for CD31 and PCNA (P < 0.01). High-dose LD and mifepristone lowered serum levels of estradiol, progesterone and LH (P < 0.05). High-dose LD, low-dose LD and mifepristone down-regulated HIF-1α mRNA and protein expressions and VEGF mRNA expression (P < 0.01). CONCLUSION:The inhibition of hysteromyoma by LD may involve reductions in HIF-1α and VEGF expression and suppression of micro-angiogenesis.