Hassoun Shimaa M, Abdel-Rahman Noha, Eladl Entsar I, El-Shishtawy Mamdouh M
1 Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
2 Department of Pathology, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Tumour Biol. 2017 Jun;39(6):1010428317707376. doi: 10.1177/1010428317707376.
Angiogenesis plays important roles in progression of hepatocellular carcinoma. The antiangiogenic mechanisms of vitexicarpine are not fully defined. Therefore, we conducted the following study to evaluate the antiangiogenic mechanism and antitumor activity of vitexicarpine in vivo model of hepatocellular carcinoma through modulation of vascular endothelial growth factor signaling pathway. Hepatocellular carcinoma was induced in Sprague Dawley rats by thioacetamide. Hepatocellular carcinoma was assessed by measuring serum alpha-fetoprotein and investigating liver sections stained with hematoxylin/eosin. Hepatocellular carcinoma rats were injected with vitexicarpine (150 mg/kg) for 2 weeks. Hepatic vascular endothelial growth factor was measured by enzyme-linked immunosorbent assay. Protein and expression of hepatic phospho-Ser473-AKT (p-AKT) and phospho-Tyr419-Src (p-Src) were determined. The apoptotic pathway was evaluated by assessment of protein expression of caspase-3. Vitexicarpine increased rats' survival time and decreased serum alpha-fetoprotein as well as it ameliorated fibrosis and massive hepatic tissue breakdown. It attenuated hepatocellular carcinoma-induced protein and gene expression of vascular endothelial growth factor, p-AKT, p-Src, and caspase-3. In conclusion, this study suggests that vitexicarpine possesses both antiangiogenic and antitumor activities through inhibition of vascular endothelial growth factor, p-AKT/AKT, and p-Src with subsequent inhibition of apoptotic pathway.
血管生成在肝细胞癌进展中发挥重要作用。牡荆素的抗血管生成机制尚未完全明确。因此，我们进行了以下研究，通过调节血管内皮生长因子信号通路，在肝细胞癌体内模型中评估牡荆素的抗血管生成机制和抗肿瘤活性。通过硫代乙酰胺诱导Sprague Dawley大鼠发生肝细胞癌。通过检测血清甲胎蛋白并观察苏木精/伊红染色的肝脏切片来评估肝细胞癌。给肝细胞癌大鼠注射牡荆素（150mg/kg），持续2周。采用酶联免疫吸附测定法检测肝血管内皮生长因子。测定肝脏磷酸化丝氨酸473-AKT（p-AKT）和磷酸化酪氨酸419-Src（p-Src）的蛋白及表达。通过评估半胱天冬酶-3的蛋白表达来评价凋亡途径。牡荆素延长了大鼠的生存时间，降低了血清甲胎蛋白水平，并改善了纤维化和大量肝组织破坏。它减弱了肝细胞癌诱导的血管内皮生长因子、p-AKT、p-Src和半胱天冬酶-3的蛋白和基因表达。总之，本研究表明牡荆素通过抑制血管内皮生长因子、p-AKT/AKT和p-Src，继而抑制凋亡途径，从而具有抗血管生成和抗肿瘤活性。
