Improvement of Blood Hypercoagulability in Mice with Colorectal Cancer by Simvastatin Based on miR-181/NF-κB Pathway

ZHANG Rui; CHANG Na; CHEN Chao; ZHAO Meng; LI Bo

doi:10.14009/j.issn.1672-2124.2022.06.013

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Improvement of Blood Hypercoagulability in Mice with Colorectal Cancer by Simvastatin Based on miR-181/NF-κB Pathway

更新时间：2022-10-08

- Improvement of Blood Hypercoagulability in Mice with Colorectal Cancer by Simvastatin Based on miR-181/NF-κB Pathway
- Vol. 22, Issue 6, Pages: 690-695(2022)
- 作者机构：
  
  1. 唐山市人民医院药剂科
  2. 唐山市人民医院放化五科唐山市肿瘤放射治疗学重点实验室
  3. 遵化市人民医院病理科
- 作者简介：
- 基金信息：
- DOI：10.14009/j.issn.1672-2124.2022.06.013
  CLC： R965
- Published：2022，
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ZHANG Rui, CHANG Na, CHEN Chao, et al. Improvement of Blood Hypercoagulability in Mice with Colorectal Cancer by Simvastatin Based on miR-181/NF-κB Pathway. [J]. 22(6):690-695(2022)
DOI：

ZHANG Rui, CHANG Na, CHEN Chao, et al. Improvement of Blood Hypercoagulability in Mice with Colorectal Cancer by Simvastatin Based on miR-181/NF-κB Pathway. [J]. 22(6):690-695(2022) DOI： 10.14009/j.issn.1672-2124.2022.06.013.

摘要

目的：基于微小RNA（miR）-181/核因子κB（NF-κB）通路，探讨辛伐他汀对结直肠癌小鼠肿瘤生长、血液高凝状态的影响。方法：选取BALB/C裸鼠，通过皮下注射人结直肠癌细胞系SW480的方法构建结直肠癌小鼠模型，将30只模型小鼠随机分为对照组、辛伐他汀低和高剂量组。辛伐他汀低、高剂量组小鼠分别腹腔注射辛伐他汀50、100 mg/kg

1日1次，第28日分析小鼠肿瘤生长、血管生成和凝血情况。通过定量反转录聚合酶链反应、蛋白质印迹法检测肿瘤组织中miR-181、NF-κB抑制蛋白α（IκBα）以及NF-κB mRNA和蛋白表达水平。结果：与对照组比较，辛伐他汀低、高剂量组小鼠的肿瘤体积和重量，细胞周期蛋白D1（CyclinD1）、Ki67和B细胞淋巴瘤2（Bcl-2）蛋白水平，微血管密度、血管内皮生长因子（VEGF）水平和全血黏度，IκBα、NF-κB mRNA和蛋白表达水平均显著降低；而Bcl-2相关X蛋白（Bax）、miR-181水平显著升高，血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）显著延长，上述差异均有统计学意义（P

0.05）。辛伐他汀高剂量组小鼠的肿瘤体积和重量、微血管密度显著低于辛伐他汀低剂量组[（171.74±19.33）mm

vs.（226.52±26.38）mm

（0.21±0.03）g vs.（0.28±0.04）g

（9.77±1.85）%vs.（16.39±2.11）%]

CyclinD1、Ki67和Bcl-2蛋白水平，VEGF水平、全血黏度，IκBα、NF-κB mRNA和蛋白表达水平显著低于辛伐他汀低剂量组；Bax蛋白、miR-181水平显著高于辛伐他汀低剂量组，PT、APTT显著长于辛伐他汀低剂量组，上述差异均有统计学意义（P

0.05）。结论：辛伐他汀可能通过调控miR-181/NF-κB途径抑制结直肠癌模型小鼠的肿瘤生长和血管生成，并缓解血液高凝状态。

Abstract

OBJECTIVE: To explore the effects of simvastatin on tumor growth

blood coagulation in mice with colorectal cancer based on microRNA（miR）-181/nuclear factor（NF）-κB pathway. METHODS: The colorectal cancer mice model was established by subcutaneous injection of human colorectal cancer cell line SW480

and 30 model mice were randomly divided into the control group

simvastatin low-dose group and simvastatin high-dose group. The simvastatin low-dose group and simvastatin high-dose group were intraperitoneally injected with 50 mg/kg and 100 mg/kg simvastatin

qd. On the 28 th day

tumor growth

angiogenesis

coagulation indicators were analyzed. The expression levels of miR-181

IκBα and NF-κB mRNA and protein in tumor tissues were detected by quantitative reverse transcription polymerase chain reaction and western blotting. RESULTS: Compared with the control group

the tumor volume

mass

CyclinD1 protein

Ki67 protein

Bcl-2 protein

microvessel density

vascular endothelial growth factor（VEGF） levels

whole blood viscosity

IκBα and NF-κB mRNA and protein expression levels of the simvastatin low-dose group and simvastatin high-dose group decreased significantly

while Bax protein and miR-181 levels increased

plasma prothrombin time（PT）

activated partial thromboplastin time（APTT） and miR-181 were prolonged significantly

with statistically significant differences（P<0.05）. The tumor volume

mass and microvascular density in simvastatin high-dose group were significantly lower than those in simvastatin low-dose group [（171.74±19.33） mm~3 vs.（226.52±26.38） mm~3

（0.21±0.03） g vs.（0.28±0.04）g

（9.77±1.85）% vs.（16.39±2.11）%]

CyclinD1

Ki67 and Bcl-2 protein levels

VEGF levels

whole blood viscosity

expression levels of IκBα and NF-κB mRNA and protein were significantly lower than those in simvastatin low-dose group; the levels of Bax protein and miR-181 were significantly higher than those of simvastatin low-dose group

PT and APTT were significantly longer than those of simvastatin low-dose group

the differences were statistically significant（P<0.05）. CONCLUSIONS: Simvastatin may inhibit tumor growth and angiogenesis in colorectal cancer model mice by regulating the miR-181/NF-κB pathway

and alleviate blood hypercoagulability.

关键词

结直肠癌辛伐他汀微小RNA-181核因子κB凝血

Keywords

Colorectal cancerSimvastatinMicroRNA-181Nuclear factor-κBCoagulation

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