Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Urology, Hainan Western Central Hospital, Danzhou, China.
Pharm Biol. 2022 Dec;60(1):1865-1875. doi: 10.1080/13880209.2022.2123931.
Sasanquasaponin (SQS) is a commonly used traditional Chinese medicine proved to have a wide range of pharmacological functions.
The objective of this study is to explore the effect and underlying mechanism of SQS in the treatment of prostate cancer (PC).
PC cell lines (22Rv1 and PC-3) were treated with SQS (0, 0.5, 1, 2, and 4 μM) for 12 or 24 h. The viability of cells was evaluated, while the mRNA and protein levels of epithelial to mesenchymal transition (EMT)-related genes in PC cell lines were measured (Groups: Control, TGF-β1, TNF-α, TGF-β1 + TNF-α, and TGF-β1 + TNF-α + SQS). The migration and invasion abilities of PC cell lines were evaluated (Groups: Control, SQS). Finally, the antitumour effect of SQS (25, 50,100, and 200 mg/kg) in BALB/c nude mice (6 weeks, 18-20 g) was evaluated (Groups: Control, Vehicle, 25, 50,100, and 200 mg/kg SQS). The study duration was 1 month.
SQS inhibited the viability and the number of colonies of 22Rv1 or PC-3 cells. The IC of SQS of 12 and 24 h in these two cells was 3.25, 1.82, 4.76, and 4.70 μM, respectively. SQS inhibited the adhesion, migration, and invasion of PC cells. It also inhibited the expression of EMT-related markers of PC cells. The PI3K/Akt/mTOR and Smad2/3 signalling pathways were activated in the process of EMT, and SQS could significantly reduce the activation of the PI3K/Akt/mTOR and Smad2/3 pathways. Finally, SQS inhibited the growth of xenograft tumours .
SQS inhibited EMT in PC by regulating the PI3K/Akt/mTOR and Smad pathways.
重楼皂苷(SQS)是一种常用的中药,已被证明具有广泛的药理作用。
本研究旨在探讨 SQS 治疗前列腺癌(PC)的作用及机制。
用 SQS(0、0.5、1、2 和 4 μM)处理 PC 细胞系(22Rv1 和 PC-3)12 或 24 h。评估细胞活力,同时测量 PC 细胞系中上皮间质转化(EMT)相关基因的 mRNA 和蛋白水平(分组:对照、TGF-β1、TNF-α、TGF-β1+TNF-α 和 TGF-β1+TNF-α+SQS)。评估 PC 细胞系的迁移和侵袭能力(分组:对照、SQS)。最后,在 BALB/c 裸鼠(6 周龄,18-20 g)中评估 SQS(25、50、100 和 200 mg/kg)的抗肿瘤作用(分组:对照、载体、25、50、100 和 200 mg/kg SQS)。研究持续 1 个月。
SQS 抑制 22Rv1 或 PC-3 细胞的活力和集落数。这两种细胞中 SQS 的 12 和 24 h IC 分别为 3.25、1.82、4.76 和 4.70 μM。SQS 抑制 PC 细胞的黏附、迁移和侵袭。它还抑制 PC 细胞 EMT 相关标志物的表达。在 EMT 过程中,PI3K/Akt/mTOR 和 Smad2/3 信号通路被激活,SQS 可显著降低 PI3K/Akt/mTOR 和 Smad2/3 通路的激活。最后,SQS 抑制异种移植瘤的生长。
SQS 通过调节 PI3K/Akt/mTOR 和 Smad 通路抑制 PC 中的 EMT。