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芪刺三灵汤通过抑制 Wnt/β-catenin 通路抑制膀胱癌生长。

Qici Sanling decoction suppresses bladder cancer growth by inhibiting the Wnt/Β-catenin pathway.

机构信息

a Department of Urology, Longhua Hospital , Shanghai , China.

b Department of Urology, Shanghai East Hospital , Shanghai , China.

出版信息

Pharm Biol. 2019 Dec;57(1):507-513. doi: 10.1080/13880209.2019.1626449.

DOI:10.1080/13880209.2019.1626449
PMID:31401919
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6713157/
Abstract

Bladder cancer, which has high recurrence, is one of the most deadly cancers in the world. Schischkin (Fabaceae) and L. (Alismataceae) are important herbs reported to be effective in cancer therapy. The efficacy of QCSL (Qici Sanling decoction) in bladder cancer treatment was examined. T24 cells were injected into the flanks of nude mice and the mice were randomly divided into five groups: control; 20 mg/kg XAV-939 (an inhibitor of the WNT/β-catenin pathway); QCSL (100, 200, or 400 mg/kg). After 7 weeks, the mice were anaesthetised using isoflurane and the xenografts were excised to perform further experiments. Both XAV-939 (tumour volume: 379.67 ± 159.92 mm) and QCSL (796.18 ± 101.6 mm) dramatically suppressed tumour growth comparing with control group (3612.12 ± 575.03 mm). XAV-939 and QCSL treatments decreased cell proliferation from 56.3 ± 0.05% to 29.02 ± 0.07% and 37.51 ± 0.04%, respectively. In agreement, more infiltration of immune cells and pyknotic cells upon XAV-939 (apoptosis rates: 43.92 ± 0.03%) and QCSL (34.57 ± 0.04%) treatment comparing with control group (15.59 ± 0.03%) were observed. Furthermore, TUNEL staining of xenograft tumours illustrated more apoptotic cells upon XAV-939 and QCSL treatment. Mechanistically, XAV-939 and QCSL treatments significantly inhibited WNT/β-catenin pathway in T24 xenograft tumours. Our findings give new insights into the role of QCSL in bladder cancer and explore potential mechanisms contributing to the therapeutic effects of QCSL in bladder cancer.

摘要

膀胱癌具有高复发率,是世界上最致命的癌症之一。 Schischkin(豆科)和 L.(泽泻科)是报告在癌症治疗中有效的重要草药。 考察了 QCSL(七次三令汤)在膀胱癌治疗中的疗效。 将 T24 细胞注入裸鼠的侧腹,将小鼠随机分为五组:对照组;20mg/kg XAV-939(WNT/β-catenin 通路抑制剂);QCSL(100、200 或 400mg/kg)。 7 周后,用异氟烷麻醉小鼠,切除异种移植物进行进一步实验。 XAV-939(肿瘤体积:379.67±159.92mm)和 QCSL(796.18±101.6mm)均显著抑制肿瘤生长与对照组(3612.12±575.03mm)相比。 XAV-939 和 QCSL 处理将细胞增殖从 56.3±0.05%降低至 29.02±0.07%和 37.51±0.04%。 同样,与对照组(凋亡率:15.59±0.03%)相比,XAV-939(凋亡率:43.92±0.03%)和 QCSL(34.57±0.04%)处理后免疫细胞和固缩细胞的浸润更多。 此外,XAV-939 和 QCSL 处理的异种移植肿瘤的 TUNEL 染色显示更多的凋亡细胞。 从机制上讲,XAV-939 和 QCSL 处理显著抑制了 T24 异种移植肿瘤中的 WNT/β-catenin 通路。 我们的研究结果为 QCSL 在膀胱癌中的作用提供了新的见解,并探讨了 QCSL 在膀胱癌治疗中发挥治疗作用的潜在机制。

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