Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-<italic style="font-style: italic">κ</italic>B Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice

Jun-fei GU; Ruo-lan SUN; Fu-yan LIU; Yan LIANG; Tian-tian LIU; Han-qing GUAN; De-cai TANG

doi:10.13422/j.cnki.syfjx.20212023

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Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice

更新时间：2021-10-14

- Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 21, Pages: 63-72(2021)
- 作者机构：
  
  南京中医药大学中医学院，中西医结合学院，南京 210046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20212023
  CLC： R22;R242;R2-031;R285.5
- Received：27 June 2021，
  
  Published Online：20 August 2021，
  
  Published：05 November 2021
- 稿件说明：
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顾俊菲,孙若岚,刘夫艳等.黄芪-莪术配伍对结肠癌原位移植瘤模型小鼠SDF-1/CXCR4/NF-κB信号通路的影响[J].中国实验方剂学杂志,2021,27(21):63-72.

GU Jun-fei,SUN Ruo-lan,LIU Fu-yan,et al.Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):63-72.
顾俊菲,孙若岚,刘夫艳等.黄芪-莪术配伍对结肠癌原位移植瘤模型小鼠SDF-1/CXCR4/NF-κB信号通路的影响[J].中国实验方剂学杂志,2021,27(21):63-72. DOI： 10.13422/j.cnki.syfjx.20212023.

GU Jun-fei,SUN Ruo-lan,LIU Fu-yan,et al.Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):63-72. DOI： 10.13422/j.cnki.syfjx.20212023.

摘要

目的

探讨黄芪-莪术抑制结肠癌原位移植瘤模型小鼠肿瘤生长的可能作用机制。

方法

运用分子对接技术预测黄芪、莪术中主要活性成分与通路靶点蛋白基质细胞衍生因子-1（SDF-1），趋化因子受体4（CXCR4），核转录因子-

B p65（NF-

B p65）的分子间相互作用。建立CT26.WT结肠癌原位移植瘤模型进行体内实验验证。将60只BALB/c雄性小鼠随机分为假手术组，模型组，5-氟尿嘧啶（5-Fu）组、黄芪-莪术低、中、高剂量组，每组10只。假手术组和模型组给予生理盐水灌胃，5-Fu组（30 mg·kg

-1

）腹腔注射，黄芪-莪术低、中、高剂量组（0.32，0.64，1.28 g·kg

-1

）灌胃。干预15 d后，完整剥离原位瘤，取肿瘤相邻结肠组织5~6 cm。测量并计算肿瘤体积，苏木素-伊红（HE）染色观察肿瘤组织及结肠组织病理学变化，蛋白免疫印迹法（Western blot）检测结肠组织中趋化因子SDF-1及其受体CXCR4，磷酸化NF-

B p65（p-NF-

B p65）蛋白表达，Western blot和实时荧光定量聚合酶链式反应（Real-time PCR）检测肿瘤组织趋化因子SDF-1及其受体CXCR4，NF-

B p65，细胞周期蛋白D

（Cyclin D

），癌基因c-Myc蛋白及mRNA表达水平。

结果

与模型组比较，5-Fu与黄芪-莪术治疗均能降低原位瘤体积（

0.05，

0.01），5-Fu组抑瘤率最高（61.38±2.34）%，黄芪-莪术中剂量组抑瘤率（43.43±3.71）%。与模型组比较，各药物组肿瘤与结肠组织的病理学改变转轻。与模型组比较，黄芪-莪术显著下调了肿瘤小鼠结肠组织SDF-1，CXCR4，p-NF-

B p65蛋白表达水平（

0.01），对肿瘤组织SDF-1，CXCR4，NF-

B p65，Cyclin D

，c-Myc的蛋白及mRNA表达明显下调（

0.05，

0.01）。

结论

黄芪-莪术能够抑制结肠癌原位移植瘤的生长，其干预机制可能与调节SDF-1/CXCR4/NF-

B信号通路中相关蛋白及其mRNA表达有关。

Abstract

Objective

To explore the possible mechanism of Astragali Radix-Curcumae Rhizoma （AC） in inhibiting tumor growth in the orthotopic transplantation model of colon cancer in mice.

Method

The molecular docking technology was used to predict the intermolecular interaction between the main active components of AC and the pathway target proteins， such as stromal cell-derived factor-1 （SDF-1）， C-X-C motif chemokine receptor 4 （CXCR4）， and nuclear factor kappa-B p65 （NF-

B p65）. The orthotopic transplantation model of CT26.WT colon cancer was established in mice for

in vivo

experimental verification. Sixty BALB/c male mice were randomly divided into a sham operation group， a model group， a 5-fluorouracil （5-Fu， 30 mg·kg

-1

） group，and low- （0.32 g·kg

-1

）， medium- （0.64 g·kg

-1

）， and high-dose （1.28 g·kg

-1

） AC groups， with 10 mice in each group. The sham operation group and the model group received normal saline by gavage. The corresponding drugs were administered by gavage in the 5-Fu group and by intraperitoneal injection in the AC groups. After intervention for 15 days， the tumor

in situ

was completely stripped， and the colon tissues 5-6 cm in length adjacent to the tumor were taken. The tumor volume was measured and calculated. The pathological changes of tumor tissues and colon tissues were observed by Hematoxylin-Eosin （HE） staining. Western blot was used to detect the protein expression of SDF-1， CXCR4， p-NF-

B p65 in colon tissues. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect SDF-1， CXCR4， NF-

B p65， Cyclin D

， oncogene c-Myc protein and mRNA expression in tumor tissues.

Result

Compared with the model group， 5-Fu and AC groups showed reduced tumor volumes

in situ

（

0.05，

0.01）， with the tumor inhibition rate in the 5-Fu group as high as （61.38±2.34）%. The tumor-inhibiting effect was optimal in the medium-dose AC group， with the tumor inhibition rate of （43.43±3.71）%. Compared with the model group， 5-Fu and AC groups showed relieved pathological changes of tumor and colon tissues. Specifically， AC down-regulated the protein expression levels of SDF-1， CXCR4， and p-NF-

B p65 in colon tissues （

0.01）， and down-regulated the protein and mRNA expression levels of SDF-1， CXCR4， NF-

B p65， Cyclin D

， and c-Myc in tumor tissues （

0.05，

0.01）.

Conclusion

AC can inhibit the growth of orthotopic transplantation tumor of colon cancer， and its intervention mechanism may be related to the regulation of related protein and mRNA expression in the SDF-1/CXCR4/NF-

B signaling pathway.

关键词

Keywords

references

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Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice

DOI：10.13422/j.cnki.syfjx.20212023

摘要

Abstract

关键词

Keywords

references