Synergistic effects of bevacizumab in combination with β-elemene on subcutaneous xenografts derived from HCT-116 human colon cancer cells

Jin-Na Li, Feng Xie, Ying Wang

Abstract

Background: To observe the effect of bevacizumab in combination with β-elemene on subcutaneous xenografts established from HCT-116 human colon cancer cells, explore the underlying mechanisms involved, and provide more options for the treatment of advanced colorectal cancer.
Methods: Mice were randomly divided into four groups: control, β-elemene, bevacizumab and combination treatment. Tumor volume was measured and the tumor inhibition rate and coefficient of drug interaction (CDI) were calculated. The pathological and morphological features of the tumor tissues were observed. Protein expression levels of ki-67, CD31, vascular endothelial growth factor (VEGF) and bcl-2 were measured by immunohistochemistry.
Results: The tumor volumes in the four groups were 0.991±0.131, 0.833±0.145, 0.563±0.131 and 0.324±0.066 cm3, respectively. The tumor inhibition rates in the β-elemene, bevacizumab and combination groups were 15.9%, 43.2% and 67.3%, respectively. The degree of tumor reduction in the combination group was the most significant (P<0.05), with a CDI of 0.697. Immunohistochemistry showed that the ki-67 proliferation indexes in the four groups were 30.06%±3.37%, 19.79%±3.75%, 27.51%±2.16% and 16.9%±1.09%, the microvessel densities (MVDs) were 45.86±9.28, 31.14±5.58, 27.57±6.11 and 12.14±3.53, the rates of positive VEGF expression were 39.48%±6.72%, 28.86%±3.54%, 25.04%±2.64% and 19.5%±2.68%, and the rates of positive bcl-2 expression were 33.95%±6.38%, 20.11%±9.49%, 24.28%±6.57% and 11.18%±2.72%, respectively. Compared with the control group, the three experimental groups displayed different degrees of reduction in the above indicators (P<0.05), with the combination group exhibiting the lowest values (P<0.05).
Conclusions: Bevacizumab exerts a synergistic effect with β-elemene in suppressing the growth of tumors derived from HCT-116 cells, and the related mechanisms may include the inhibition of tumor cell proliferation and tumor angiogenesis and the promotion of tumor cell apoptosis.