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.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary type of liver cancer
This study showed that the Sorafenib-only group effectively reduced vascular endothelial growth factor (VEGF) tissue level better than without the treatment group
There was no significant difference in reducing Micro-vessel density (MVD) expression compared to the combination of lowdose Sorafenib and EGCG group, which indicated better overall results than the Sorafenib-only group
Summary
Hepatocellular carcinoma (HCC) is the most common primary type of liver cancer. In 2013, the prevalence of liver and bile duct cancer in a developed country like the United States was 30,640.1,2 a high incidence of HCC was discovered in South and East Asia, Central and West Africa, Melanesia, and Micronesia/Polynesia. Micro-vessel density (MVD) is a tumor indicator of angiogenesis that needs to be examined in HCC since a higher level of MVD shows a poor prognosis. This high angiogenic activity can be inhibited through the administration of anti-angiogenic drugs.[8]. Author’s comment: Yes, they referred to the same reference. 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. The level of vascular endothelial growth factor (VEGF) and expression of microvascular density was examined using liver tissues. 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.
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