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丹皮酚通过诱导细胞凋亡诱导膀胱癌细胞死亡,并延缓小鼠膀胱肿瘤生长。

Cortex Moutan Induces Bladder Cancer Cell Death via Apoptosis and Retards Tumor Growth in Mouse Bladders.

机构信息

Graduate Institute of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Chinese Medicine, Chiayi Christian Hospital, Chiayi 60002, Taiwan.

出版信息

Evid Based Complement Alternat Med. 2013;2013:207279. doi: 10.1155/2013/207279. Epub 2013 Oct 24.

Abstract

Cortex Moutan is the root bark of Paeonia suffruticosa Andr. It is the herbal medicine widely used in Traditional Chinese Medicine for the treatment of blood-heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex Moutan has anticancer effect. In this study, the Cortex Moutan extract was evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract reduces cell viability with IC50 between 1~2 mg/ml in bladder cancer cells, and it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S phase and causes phosphatidylserine expression in the outside of cell membrane. It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan decreases the bladder tumor size without altering the blood biochemical parameters. In summary, these results demonstrate the antiproliferation and anti-invasion properties of Cortex Moutan in bladder cancer cells and its antibladder tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer.

摘要

牡丹皮是牡丹 Paeonia suffruticosa Andr. 的根皮,是一种广泛应用于中医治疗血热血瘀综合征的草药。此外,已有报道称牡丹皮具有抗癌作用。在这项研究中,牡丹皮提取物在膀胱癌的体内和体外治疗中进行了评估。牡丹皮提取物在膀胱癌细胞中使细胞活力降低的 IC50 在 1~2mg/ml 之间,对正常尿路上皮的细胞毒性较低。它使细胞停滞在 G1 和 S 期,并导致细胞膜外的磷脂酰丝氨酸表达。它诱导半胱氨酸天冬氨酸蛋白酶-8 和半胱氨酸天冬氨酸蛋白酶-3 的激活和多聚(ADP-核糖)聚合酶的降解。半胱氨酸天冬氨酸蛋白酶抑制剂 z-VAD-fmk 逆转了牡丹皮诱导的细胞死亡。牡丹皮还抑制了 5637 细胞的细胞侵袭活性。在小鼠原位膀胱癌模型中,膀胱内应用牡丹皮可减小膀胱肿瘤的大小,而不改变血液生化参数。总之,这些结果表明牡丹皮在膀胱癌细胞中的增殖和侵袭抑制特性及其在体内的抗膀胱癌作用。牡丹皮可能为浅表膀胱癌的膀胱内治疗提供一种替代的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ced/3824643/153c3d2b439c/ECAM2013-207279.001.jpg

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