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延龄草甾体皂苷在体外和体内抑制结直肠癌细胞的生长。

Trillium tschonoskii steroidal saponins suppress the growth of colorectal Cancer cells in vitro and in vivo.

机构信息

Department of Pharmacy, Xijing Hospital, the Fourth military medical university, Xi'an 710032, Shaanxi, PR China; No. 422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China.

No. 422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China.

出版信息

J Ethnopharmacol. 2015 Jun 20;168:136-45. doi: 10.1016/j.jep.2015.03.063. Epub 2015 Apr 4.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Saponins of many herbs are known to possess anti-cancer effect.

AIM OF THE STUDY

The present study aimed to investigate the growth inhibitory effect of Trillium tschonoskii steroidal saponins in a mouse model of colitis-associated colorectal cancer and a human colorectal cancer cell line HT-29, and isolate some major constituents and evaluate their anti-tumor activity.

MATERIALS AND METHODS

Forty male ICR mice were administered with 1, 2-dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Ten mice were given no further treatment, the rest were administered with different doses of TTS (5, 10, 20mg/kg) orally, every three days from the 9th week to the 20th week.

RESULTS

TTS effectively protected ICR mice against DMH/DSS-induced tumorigenesis. The incidence of tumor development was 90% (9/10) in the mice treated with DMH/DSS, but that was reduced to 50% (5/10), 40% (4/10), and 20% (2/10), respectively, in the mice treated with 5%, 10%, and 20% of TTS. Results of Ki-67 staining, TUNEL assay and caspase-3 activity assay revealed that TTS moderately decreased abnormal proliferation and increased apoptosis of colonic epithelial cells. It inhibited the growth and triggered the apoptosis of HT-29 cells, partly through suppressing mitogen-actived protein kinases (MAPKs) and triggering mitochondrial-mediated apoptotic pathway. Three compounds, namely, Paris saponin VII, polyphylloside III and Paris saponin VI, were important active compounds in TTS.

CONCLUSION

These data suggest that TTS has a potential role in clinical prevention and treatment for colorectal cancer.

摘要

民族药理学相关性

许多草药的皂苷已被证明具有抗癌作用。

研究目的

本研究旨在探讨延龄草甾体皂苷(TTS)在结肠炎相关结直肠癌小鼠模型和人结肠癌细胞系 HT-29 中的生长抑制作用,并分离一些主要成分并评估其抗肿瘤活性。

材料和方法

40 只雄性 ICR 小鼠给予 1,2-二甲基肼(DMH)和葡聚糖硫酸钠(DSS)。10 只小鼠未进行进一步治疗,其余小鼠分别给予 TTS(5、10、20mg/kg)口服,从第 9 周到第 20 周每三天一次。

结果

TTS 可有效保护 ICR 小鼠免受 DMH/DSS 诱导的肿瘤发生。用 DMH/DSS 处理的小鼠中肿瘤发展的发生率为 90%(9/10),但用 5%、10%和 20%的 TTS 处理的小鼠中分别降低至 50%(5/10)、40%(4/10)和 20%(2/10)。Ki-67 染色、TUNEL 检测和 caspase-3 活性检测结果表明,TTS 可适度降低结肠上皮细胞的异常增殖并增加细胞凋亡。它抑制 HT-29 细胞的生长并引发其凋亡,部分通过抑制丝裂原激活蛋白激酶(MAPKs)和触发线粒体介导的凋亡途径。三种化合物,即重楼皂苷 VII、重楼皂苷 III 和重楼皂苷 VI,是 TTS 中的重要活性化合物。

结论

这些数据表明 TTS 可能在结直肠癌的临床预防和治疗中发挥作用。

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