The effect of Epigallocatechin-3-Gallate (EGCG) combined with low dose sorafenib in apoptosis and Platelet-Derived Growth Factor Receptor (PDGFR) expression in hepatocellular carcinoma rats

Abstract

Background: Sorafenib is a targeting therapy in Hepatocellular carcinoma (HCC) that targets Vascular Endothelial Growth Factor Receptors 1 (VEGFR-1), VEGFR-2, and VEGFR-3; Platelet-Derived Growth Factor Receptors β (PDGFR-β); c-Kit proto-oncogenes; FLT-3 genes; RET proto-oncogenes; and Raf-1 genes that have the same function in suppressing tumor cell proliferation, angiogenesis, and promotes tumor cell apoptosis; but its high cost makes necessary to reduce the dosage by combining with other agents. Epigallocatechin-3-Gallate (EGCG) has great potential in cancer treatment because of its anti-angiogenesis, induced apoptosis, and low cost. This study aimed to examine the effects of combination EGCG with low dose sorafenib compared to standard dose sorafenib in apoptosis and PDGFR expression in HCC rats Methods: Twenty-five male Wistar rats were randomly assigned into 4 groups: sham, control, EGCG+low dose sorafenib, and standard-dose sorafenib. Diethylnitrosamine (DEN) injection to induce HCC was carried out to all Wistar rats except for the sham group. After HCC was developed, the EGCG+low dose sorafenib group and standard-dose sorafenib group received the administration of the drugs for two weeks. PDGFR expression and apoptotic index were assessed in the last 3 groups. Data were analyzed using SPSS version 20 for Windows. Results: There was a non-significant difference of mean PDGFR expression level between the EGCG+low dose sorafenib group and standard-dose sorafenib group (p>0.05); however, there was a lower significant difference of both groups compared to the control group (p<0.05). There was a non-significant difference of apoptotic index between low dose sorafenib+EGCG group and standard-dose sorafenib group (p>0.05); in addition, there were a higher not significantly different of both groups compared to the control group (p>0.05). Conclusion: Combining low dose sorafenib with EGCG has a comparable effect with standard-dose sorafenib in reducing PDGFR of HCC, but not for apoptosis.