Effect of cinobufacin combined with As2O3 on the angiogenesis of subcutaneous colorectal carcinoma transplantation tumor in BALB/C nude mice
10.3760/cma.j.issn.1006-9801.2019.12.002
- VernacularTitle: 华蟾素联合三氧化二砷对BALB/C裸鼠皮下结肠癌移植瘤血管生成的影响
- Author:
Xia LIU
1
;
Zhengjie HAN
;
Tingting LIU
;
Jie LIU
;
Liyong GAO
Author Information
1. Department of Pathology, Xuzhou No.1 People's Hospital, Xuzhou 221000, China
- Publication Type:Journal Article
- Keywords:
Colonic neoplasms;
Cinobufacin;
Arsenites;
Nude mice;
Angiogenesis
- From:
Cancer Research and Clinic
2019;31(12):799-804
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of cinobufacin combined with As2O3 on the angiogenesis of subcutaneous transplantation tumor in colorectal carcinoma BALB/C nude mice.
Methods:The colorectal carcinoma transplantation tumor model of BALB/C nude mice was established and divided into 4 groups, 5 mice in each group. The growth state of nude mice was observed by injecting the corresponding reagents into the tumor in As2O3 group, cinobufacin group, cinobufacin combined As2O3 group and the blank control group (replaced by phosphate buffer), respectively. The nude mice were killed two weeks later, and the tumor tissues, liver and kidney tissues and orbital vein blood were taken. The tumor volume inhibition rate and mass inhibition rate of nude mice were calculated. The histomorphology of tumor, liver and kidney and blood routine were detected. The expressions of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), fibroblast growth factor-basic (b-FGF) and CD105 in transplanted tumor tissues were detected by using immunohistochemistry method, and the microvascular density (MVD) of transplanted tumor in nude mice was evaluated. Western blot method was used to detect the protein expression levels of VEGF, EGFR and b-FGF.
Results:After 2 weeks of administration, the tumor volume and tumor mass in As2O3 group, cinobufacin group and cinobufacin combined As2O3 group were lower than those in the blank control group. The volume inhibition rate was 16%, 17%, 72%, and the mass inhibition rate was 31%, 33%, 78%, respectively, and the difference was statistically significant (all P < 0.01); there was no statistical difference between As2O3 group and cinobufacin group in the tumor volume and tumor mass (P > 0.05), and cinobufacin combined As2O3 group had the most obvious therapeutic effects (all P < 0.05). The immunohistochemistry method showed that the expressions of VEGF, EGFR, b-FGF and MVD were decreased in As2O3 group, cinobufacin group and cinobufacin combined As2O3 group compared with the blank control group, and there were statistical differences of the four groups (all P < 0.05). There was no statistical difference of the marker changes in As2O3 group and cinobufacin group (all P > 0.05), and cinobufacin combined As2O3 group had the most significant decrease in the marker changes, and there was a significant difference compared with the other groups (all P < 0.05). Western blot showed that compared with the blank control group, the other three groups could downregulate the protein expressions of VEGF, EGFR and b-FGF in the transplanted tumor of nude mice. And the decreasing expression of each protein in cinobufacin combined As2O3 group was the most significant. Pathomorphology examination showed that the histomorphology of liver and kidney of the four groups of nude mice was normal. Blood routine examination showed that compared with the blank control group, the white blood cell count of nude mice in other groups was decreased, and the difference was statistically significant (all P < 0.05). The white blood cell count of cinobufacin combined As2O3 group was decreased most significantly; there was no statistically significant difference in hemoglobin and platelet count among the four groups (all P > 0.05).
Conclusions:Cinobufacin and As2O3 show synergistic effects in the tumor angiogenesis and inhibition of transplantation tumor growth of colorectal cancer BALB/C nude mice. Moreover, cinobufacin and As2O3 have no obvious toxicity to the hepatic, kidney and hematopoietic tissues.
