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补骨脂酚通过与雄激素非依赖性前列腺癌细胞 PC-3 中的 AR 和 ERβ 的 NF-κB 交叉对话信号传导发挥抗转移活性。

Bakuchiol exhibits anti-metastasis activity through NF-κB cross-talk signaling with AR and ERβ in androgen-independent prostate cancer cells PC-3.

机构信息

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin, 300193, China.

Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin, 300193, China.

出版信息

J Pharmacol Sci. 2018 Sep;138(1):1-8. doi: 10.1016/j.jphs.2017.04.004. Epub 2017 Jun 16.

Abstract

Androgen-independent prostate cancer (PCa) is a developed tumor derived from the local androgen dependent PCa, which often affects elderly men. Psoralea corylifolia L, a traditional Chinese medicine, has been widely used for PCa treatment as an important part of a common prescription, while the mechanism remains unclear. Our study was aimed to investigate the tumor-inhibitory effect of its main component bakuchiol in androgen-independent PCa cell line PC-3 cells. Bakuchiol significantly suppressed PC-3 cell proliferation and migration; the expressions of PCNA and MMP-9 were consistently down regulated as well. Meanwhile, both the constitutive and LPS-induced NF-κB activation were significantly inhibited by bakuchiol. The inhibitory effects of bakuchiol on cell proliferation, migration and invasion were recovered when LPS were added together with bakuchiol. SiRNA against androgen receptor (AR) or estrogen receptor β (ERβ) were transfected and the regulation of bakuchiol-suppressed proliferation, invasion, NF-κB signaling and MMP-9 secretion in response to LPS were blocked. Taken together, our data demonstrated that bakuchiol inactivated NF-κB signaling via AR and ERβ, which contributes to inhibition of PC-3 cell proliferation and migration, indicating that bakuchiol is one of the key component from P. corylifolia L for PCa treatment and has a potential as anti-prostate cancer drug candidates.

摘要

雄激素非依赖性前列腺癌(PCa)是一种源于局部雄激素依赖性 PCa 的发展性肿瘤,常发生于老年男性。补骨脂素是一种传统的中药,已被广泛用于治疗 PCa,作为常见处方的重要组成部分,但其机制尚不清楚。我们的研究旨在探讨其主要成分补骨脂素在雄激素非依赖性 PCa 细胞系 PC-3 细胞中的肿瘤抑制作用。补骨脂素显著抑制 PC-3 细胞的增殖和迁移;PCNA 和 MMP-9 的表达也持续下调。同时,补骨脂素显著抑制了 NF-κB 的组成性和 LPS 诱导性激活。当 LPS 与补骨脂素一起添加时,补骨脂素对细胞增殖、迁移和侵袭的抑制作用得到恢复。转染雄激素受体(AR)或雌激素受体β(ERβ)的 siRNA,并阻断了 LPS 对增殖、侵袭、NF-κB 信号和 MMP-9 分泌的抑制作用。综上所述,我们的数据表明,补骨脂素通过 AR 和 ERβ 使 NF-κB 信号失活,从而抑制 PC-3 细胞的增殖和迁移,表明补骨脂素是 P. corylifolia L 治疗 PCa 的关键成分之一,具有作为抗前列腺癌药物候选物的潜力。

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