Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA.
Int J Mol Sci. 2023 Jun 21;24(13):10465. doi: 10.3390/ijms241310465.
Tranilast (N-3, 4-dimethoxycinnamoyl anthranilic acid) is an orally administered drug with antiallergic properties and approved in Japan and the Republic of Korea for the treatment of asthma and hypertrophic scars. Previous in vitro studies indicated that tranilast reduced fibroid growth through its inhibitory effects on cell proliferation and induction of apoptosis. The objective of this study was to determine the efficacy of tranilast for treatment of human-derived fibroids in a mouse model. SCID mice (ovariectomized, supplemented with estrogen and progesterone) were implanted with fibroid explants and treated for two months with tranilast (50 m/kg/daily) or the vehicle. After sacrifice, xenografts were excised and analyzed. Tranilast was well tolerated without adverse side effects. There was a 37% reduction in tumor weight along with a significant decrease in staining for Ki67, CCND1, and E2F1; a significant increase in nuclear staining for cleaved caspase 3; and reduced staining for TGF-β3 and Masson's trichrome in the tranilast treated mice. There was a significant inhibition of mRNA and protein expression of fibronectin, COL3A1, CCND1, E2F1, and TGF-β3 in the xenografts from the tranilast-treated mice. These promising therapeutic effects of tranilast warrant additional animal studies and human clinical trials to evaluate its efficacy for treatment of fibroids.
曲尼司特（N-3,4-二甲氧基肉桂酰基-邻氨基苯甲酸）是一种口服药物，具有抗过敏特性，在日本和韩国被批准用于治疗哮喘和增生性瘢痕。先前的体外研究表明，曲尼司特通过抑制细胞增殖和诱导细胞凋亡来减少纤维瘤的生长。本研究的目的是确定曲尼司特在小鼠模型中治疗人源性纤维瘤的疗效。SCID 小鼠（卵巢切除，补充雌激素和孕激素）植入纤维瘤外植体，并接受曲尼司特（50mg/kg/天）或载体治疗两个月。处死动物后，切除异种移植物并进行分析。曲尼司特耐受性良好，无不良反应。肿瘤重量减轻了 37%，Ki67、CCND1 和 E2F1 的染色显著减少；cleaved caspase 3 的核染色显著增加；曲尼司特治疗小鼠的 TGF-β3 和 Masson 三色染色减少。曲尼司特治疗的异种移植物中纤维连接蛋白、COL3A1、CCND1、E2F1 和 TGF-β3 的 mRNA 和蛋白表达均受到显著抑制。曲尼司特的这些有前景的治疗效果需要进一步的动物研究和人类临床试验来评估其治疗纤维瘤的疗效。
