Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice
10.13422/j.cnki.syfjx.20212023
- VernacularTitle: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
- Author:
Jun-fei GU
1
;
Ruo-lan SUN
1
;
Fu-yan LIU
1
;
Yan LIANG
1
;
Tian-tian LIU
1
;
Han-qing GUAN
1
;
De-cai TANG
1
Author Information
1. School of Chinese Medicine， School of Integrated Chinese and Western Medicine， Nanjing University of Chinese Medicine， Nanjing 210046， China
- Publication Type:Research Article
- Keywords:
colon cancer;
Astragali Radix-Curcumae Rhizoma;
stromal cell-derived factor-1 （SDF-1）/C-X-C motif chemokine receptor 4 （CXCR4）/nuclear factor kappa-B （NF-κB）;
molecular docking
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(21):63-72
- CountryChina
- Language:Chinese
-
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-κB 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-κB p65 in colon tissues. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect SDF-1， CXCR4， NF-κB p65， Cyclin D1， 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 （P<0.05， P<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-κB p65 in colon tissues （P<0.01）， and down-regulated the protein and mRNA expression levels of SDF-1， CXCR4， NF-κB p65， Cyclin D1， and c-Myc in tumor tissues （P<0.05， P<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-κB signaling pathway.
