Wang Chao, Du Xiaoling, Yang Rui, Liu Jie, Xu Da, Shi Jiandang, Chen Linfeng, Shao Rui, Fan Guanwei, Gao Xiumei, Tian Guo, Zhu Yan, Zhang Ju
Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071, China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
J Steroid Biochem Mol Biol. 2015 Jan;145:28-37. doi: 10.1016/j.jsbmb.2014.09.026. Epub 2014 Oct 5.
Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in elderly men. Tanshinone IIA (Tan IIA) is the active ingredient extracted from the traditional Chinese medicine Salvia, and it has effects of anti-oxidation, anti-inflammation, vascular smooth muscle relaxation and tumour growth inhibition. The present study aimed to investigate the therapeutic potential of Tan IIA in the prevention and treatment of BPH. In a rat model of oestradiol/testosterone-induced BPH, Tan IIA inhibited the increase in the thickness of the peri-glandular smooth muscle layer, suppressed the expression of proliferating cell nuclear antigen (PCNA) in both prostate epithelial cells and stromal cells, downregulated the expression of androgen receptor (AR), oestrogen receptor α (ERα), cyclin B1 (CCNB1) and cyclin D1 (CCND1), and effectively prevented the development of the disorder. In vitro, Tan IIA inhibited the proliferation of human prostate stromal cell line WPMY-1 and epithelial cell line RWPE-1 in a dose- and time-dependent manner. In WPMY-1 cells, Tan IIA treatment arrested the cell cycle at the G2/M phase and downregulated the expression of CCNB1. However, in RWPE-1 cells, Tan IIA treatment arrested cell cycle at the G0/G1 phase and reduced the expression of CCND1. Tan IIA also reduced the expression of ERα and AR in WPMY-1 and RWPE-1 cells. These results suggest that Tan IIA can inhibit the growth of prostate stromal and epithelial cells both in vivo and in vitro by a mechanism that may involve arresting the cell cycle and downregulating ERα and AR expression.
良性前列腺增生(BPH)是老年男性泌尿系统的主要疾病之一。丹参酮IIA(Tan IIA)是从传统中药丹参中提取的活性成分,具有抗氧化、抗炎、血管平滑肌舒张和抑制肿瘤生长的作用。本研究旨在探讨Tan IIA在预防和治疗BPH方面的治疗潜力。在雌二醇/睾酮诱导的BPH大鼠模型中,Tan IIA抑制腺周平滑肌层厚度的增加,抑制前列腺上皮细胞和基质细胞中增殖细胞核抗原(PCNA)的表达,下调雄激素受体(AR)、雌激素受体α(ERα)、细胞周期蛋白B1(CCNB1)和细胞周期蛋白D1(CCND1)的表达,并有效预防疾病的发展。在体外,Tan IIA以剂量和时间依赖性方式抑制人前列腺基质细胞系WPMY-1和上皮细胞系RWPE-1的增殖。在WPMY-1细胞中,Tan IIA处理使细胞周期停滞在G2/M期,并下调CCNB1的表达。然而,在RWPE-1细胞中,Tan IIA处理使细胞周期停滞在G0/G1期,并降低CCND1的表达。Tan IIA还降低了WPMY-1和RWPE-1细胞中ERα和AR的表达。这些结果表明,Tan IIA可通过可能涉及使细胞周期停滞以及下调ERα和AR表达的机制,在体内和体外抑制前列腺基质细胞和上皮细胞的生长。