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腾龙补中颗粒抑制人结肠癌细胞 SW620 的生长。

Tenglong Buzhong granules inhibits the growth of SW620 human colon cancer.

机构信息

Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

2 Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

出版信息

J Tradit Chin Med. 2022 Oct;42(5):701-706. doi: 10.19852/j.cnki.jtcm.2022.05.004.

DOI:10.19852/j.cnki.jtcm.2022.05.004
PMID:36083476
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9924744/
Abstract

OBJECTIVE

To observe the anticancer effects of the granular preparation of Tenglong Buzhong decoction (,TBD), i.e Tenglong Buzhong granules (, TBG), in human SW620 colon cancer.

METHODS

BALB/c nude mice were subcutaneously transplanted with SW620 cells, and treated with TBG (2.56 g/kg, once per day) and/or 5-Fu (104 mg/kg, once per week) for 21 d. Apoptosis, Caspase activities and cellular senescence were measured by commercial kits. The protein expression and phosphorylation were detected by Western blot or immunohistochemistry.

RESULTS

TBG and 5-Fu inhibited tumor growth. The tumor inhibition rate of the TBG, 5-Fu, and TBG+5-Fu groups was 42.25%, 51.58%, and 76.08%, respectively. Combination of TBG and 5-Fu showed synergetic anti-cancer effects. TBG and 5-Fu induced apoptosis, activated caspase-3, -8, and -9, increased SMAC expression, inhibited XIAP expression. TBG induced cellular senescence, upregulated cyclin-dependent kinase inhibitor 1a (CDKN1a) and cyclin-dependent kinase inhibitor 2a (CDKN2a) expression, and inhibited phosphorylation of retinoblastoma-associated protein (RB) and expression of cyclin E1 (CCNE1) and cyclin-dependent kinases (CDK) 2. TBG also inhibited angiogenesis accompanied by downregulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α).

CONCLUSIONS

TBG inhibits SW620 colon cancer growth, induces apoptosis SMAC-XIAP-Caspases signaling, induces cellular senescence through CDKN1a/CDKN2a-RB-E2F signaling, inhibits angiogenesis by down-regulation of HIF-1α and VEGF, and enhances the effects of 5-Fu.

摘要

目的

观察腾龙补中汤颗粒(TBD)即腾龙补中颗粒(TBG)对人 SW620 结肠癌细胞的抗癌作用。

方法

BALB/c 裸鼠皮下接种 SW620 细胞,分别用 TBG(2.56 g/kg,每日一次)和/或 5-Fu(104 mg/kg,每周一次)处理 21 天。采用试剂盒检测细胞凋亡、半胱天冬酶活性和细胞衰老。采用 Western blot 或免疫组化检测蛋白表达和磷酸化。

结果

TBG 和 5-Fu 抑制肿瘤生长。TBG、5-Fu 和 TBG+5-Fu 组的肿瘤抑制率分别为 42.25%、51.58%和 76.08%。TBG 和 5-Fu 联合使用具有协同抗癌作用。TBG 和 5-Fu 诱导细胞凋亡,激活 caspase-3、-8 和 -9,增加 SMAC 表达,抑制 XIAP 表达。TBG 诱导细胞衰老,上调细胞周期蛋白依赖性激酶抑制剂 1a(CDKN1a)和细胞周期蛋白依赖性激酶抑制剂 2a(CDKN2a)的表达,抑制视网膜母细胞瘤相关蛋白(RB)的磷酸化和细胞周期蛋白 E1(CCNE1)和细胞周期蛋白依赖性激酶(CDK)2 的表达。TBG 还抑制血管生成,同时下调血管内皮生长因子(VEGF)和缺氧诱导因子-1α(HIF-1α)的表达。

结论

TBG 抑制 SW620 结肠癌细胞生长,通过 SMAC-XIAP-Caspases 信号通路诱导细胞凋亡,通过 CDKN1a/CDKN2a-RB-E2F 信号通路诱导细胞衰老,通过下调 HIF-1α 和 VEGF 抑制血管生成,并增强 5-Fu 的作用。