Anti-angiogenic effect of the combination low-dose sorafenib and EGCG in HCC-induced Wistar rats

Abstract

Background:  Sorafenib is an expensive standard drug used for advanced hepatocellular carcinoma. Its combination with epigallo-3-catechin gallate leads to a reduced cost but equally effective anti-angiogenic effect. Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate. Methods:  A total of 25 male Wistar rats (7-weeks-old) were randomly divided into 4 groups, namely Sham (K), Control (O), combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg/kg bodyweight (BW) intraperitoneally for 10 weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for 2 weeks. Subsequently, the level of vascular endothelial growth factor (VEGF) and expression of microvascular density was examined using liver tissues. Results: There was a significant difference (p=0.007) in the level of VEGF between the group X1 (106,682 ± 41,024) and X2 (214,5162 ± 67,71652). However, the differences in VEGF level of group X1 and X2 compared to group O (318,101 ± 55,078) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 (36 ± 4,416) and X2 (26,2 ± 4,55) was not significantly different. Meanwhile, a significant difference (p<0.05) was discovered when both groups were compared with group O (176 ± 19). Conclusion: The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib as well as the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity to reduce the expression of microvascular density.