Effect of cinobufacin combined with As2O3 on the angiogenesis of subcutaneous colorectal carcinoma transplantation tumor in BALB/C nude mice

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 0.05), and cinobufacin combined As2O3 group had the most obvious therapeutic effects (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). 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. Key words: Colonic neoplasms; Cinobufacin; Arsenites; Nude mice; Angiogenesis