The effect of Shendan Sanjie capsule on angiogenesis in mice with colitis associated cancer and mechanism
10.3760/cma.j.cn112152-20210318-00240
- VernacularTitle:参丹散结胶囊对炎症相关性结直肠癌小鼠血管生成的影响及机制
- Author:
Lesi XIE
1
;
Tong HUAN
;
Junlin YANG
;
Jian WU
;
Pan ZHAO
Author Information
1. 浙江大学医学院附属杭州市第一人民医院病理科 310006
- Keywords:
Danshensanjie capsule;
Colitis associated cancer;
Serine threonine kinase;
Hypoxia-inducible factor-1α;
Vascular endothelial growth factor A
- From:
Chinese Journal of Oncology
2021;43(11):1170-1176
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects and the mechanism of Shendansanjie capsules on angiogenesis of colitis associated cancer(CAC) mice.Methods:Azoxymethane and dextran sulfact sodium were used to construct a mice model with CAC. Ten mice were divided into the normal group, model group, Shendan Sanjie capsule group, MK-2206 group, and Shendan Sanjie capsule + IGF-1 group, respectively. Immunohistochemistry was used to detect the microvessel density (MVD) in the colon tissue of each group of mice. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the mRNA levels of basic fibroblast growth factor (bFGF) and angiopoietin 2 (Ang2) in colon tissue. Western blot was used to detect the expressions of Akt, p-Akt, vascular endothelial growth factor A (VEGFA), hypoxia-inducible factor-1α (HIF-1α).Results:The number of MVD in the colon tissue of mice in the model group, Shendan Sanjie capsule group, MK-2206 group, Shendan Sanjie capsule + IGF-1 group were 63.3±3.3, 36.6±2.3, 36.6±2.2, 50.3±2.5, significantly higher than 2.0±0.1 in the normal group ( P<0.05). The number of MVD in Shendan Sanjie capsule group, MK-2206 group and Shendan Sanjie capsule+ IGF-1 group are lower than that in model group ( P<0.05), while Shendan Sanjie capsule+ IGF-1 group is higher than Shendan Sanjie Capsule group ( P<0.05). The relative expressions of bFGF mRNA in the colon cancer tissue of mice in the model group, Shendan Sanjie capsule group, MK-2206 group and Shendan Sanjie capsule+ IGF-1 group were 4.55±0.31, 2.46±0.37, 2.49±0.33, 3.34±0.21, respectively, and the relative mRNA expressions of Ang2 were 5.78±0.19, 2.21±0.14, 2.26±0.17 and 3.67±0.32, respectively, which were significantly higher than 1.01±0.05 and 0.99±0.07 in the normal group ( P<0.05). The mRNA levels of bFGF and Ang2 in Shendan Sanjie capsule group, MK-2206 group and Shendan Sanjie capsule+ IGF-1 group were lower than those in the model group ( P<0.05), while Shendan Sanjie capsule+ IGF-1 group is higher than Shendan Sanjie capsule group ( P<0.05). The relative expression levels of p-Akt/Akt, VEGFA and HIF-1α in colon cancer tissues of the model group were 4.75±0.18, 4.64±0.22 and 4.84±0.12, respectively, which were significantly higher than 1.01±0.07, 0.95± 0.08 and 0.98±0.05 in the normal group ( P<0.05). The relative expressions of p-Akt/Akt, VEGFA and HIF-1α in colon cancer tissues in the Shendan Sanjie capsule group were 2.24±0.22, 3.15±0.26 and 2.07±0.18, respectively, which were significantly lower than those in the model group ( P<0.05). However, compared with the MK-2206 group, the difference was not statistically significant ( P>0.05). The relative expression levels p-Akt/Akt, VEGFA and HIF-1α in colon cancer tissue of the Shendan Sanjie capsule+ IGF-1 group were 3.37±0.15, 4.02±0.11, 3.52±0.24, respectively, which were significantly higher than those in the Shendan Sanjie capsule group ( P<0.05). Conclusion:Shendan Sanjie capsules may inhibit Akt/HIF-1α/VEGFA signaling pathway, and then reduce the expression of microvascular growth factors bFGF and Ang2, thereby inhibit the tumor angiogenesis of CAC.
