Hepatic arterial infusion of 3-bromopyruvate to block up the energy metabolism of hepatic carcinoma: an experimental study in rats

Objective To assess the antitumor effect of 3-bromopyruvate on Walker256 cells, and to evaluate hepatic arterial infusion of 3-bromopyruvate in treating hepatocellular carcinoma in rat models.Methods MTT assay was applied to detect the antitumor activity of 3-bromopyruvate on Walker256 cells,and cell apoptosis was analyzed by using DNA ladder experiment in vitro. Walker256 carcinoma was implanted in the liver of rats to establish the tumor models. Rats in experimental groups(group A, n = 10)received arterial infusion of 3-bromopyruvate(1 ml in a 1.5 mg/kg concentration), rats in negative control group(group B, n = 6) received hepatic arterial infusion of saline(1 ml), and rats in positive control group(group C, n = 6) received infusion of mitomycin(0.1 mg) as well as embolization with Lipiodol(0.1 ml).Tumor volume was measured by MRI on the day before interventional treatment and the third day after interventional treatment. After completion of the MRI examination, all the rats were sacrificed, and the proportion of tumor necrosis was calculated based on histopathologic examination. Results The inhibition rates of Walker256 cells treated with 1, 5, 10, 25 and 50 mmol/L 3-bromopyruvate were(10.9 ± 0.9)%,(18.5 ± 1.7)%,(24.2 ± 1.3)%,(40.4 ±3.0)% and(55.1 ± 2.4)% respectively, and50 mmol/L of 3-bromopyruvate could induce cell apoptosis. The mean tumor volume of group A, B and C after treatment was (482.98 ± 103.88) mm3,(432.44 ± 437.39) mm3and(569.79 ± 268.89) mm3, respectively. No significant difference in tumor volume existed between each other among the three groups(P 0.05). In group A, tumor necrosis grade Ⅲ was seen in 7 rats, grade Ⅳ in 2 rats and grade Ⅰ in one rat. In group B, all 6 rats showed grade Ⅰ necrosis. In group C, tumor necrosis grade Ⅲ was seen in 5 rats and grade Ⅱ in one rat. The mean tumor necrosis rate of group A was significantly higher than that of group B(P = 0.001), and no significant difference in mean tumor necrosis rate existed between group A and group C(P = 0.927). Conclusion The tumor energy metabolism blocking up agent, 3-bromopyruvate, carries strong antitumor effect both in vivo and in vitro.