Objective To investigate the effect and mechanism of iridoid glycoside from Boschniakia rossica (IGBR) on diethylnitrosamine (DEN)-induced apoptosis of rat liver cancer cells.
Methods Totally 132 male Wistar rats were randomly assigned into 4 groups for a 28-week experiment: a liver cancer model group, 5-fluorouracil (5-FU) group with intraperitoneal injection of 25 mg/kg 5-FU 3 times a week, IGBR group with daily gavage of 500 mg/kg, and a control group; all the rats were injected intraperitoneally with 200 mg/kg DEN on the first day of the experiment and then supplied with 0.05% DEN solution as drinking water throughout the experiment, except for those of control group only with the injection of saline. The animals were sacrificed in batches by the end of 12-, 20- and 28-week of the experiment. The apoptosis of liver cells was detected with terminal transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL); the expressions of signal pathway related protein, including B-cell lymphoma 2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) were determined with Western blot.
Results The apoptosis index (AI) of the model group was 12.3 ± 0.4% and significantly higher than that of the control group; the AI of 5-FU and IGBR group were 22.2 ± 0.1% and 22.3 ± 0.2%, significantly higher than that of the model group (both P < 0.05), but the AI was not significantly different between 5-FU and IGBR group (P > 0.05). Compared with those of the control group, the expressions of phosphorylated extracellular-signal-regulated kinase (p-ERK) and phosphorylated Akt (p-Akt) reduced but phosphorylated c-Jun amino-terminal kinase (p-JNK) and phosphorylated p38 (p-p38) increased; while ERK, p38, JNK, and Akt did not vary obviously in liver tissues of model group. Decreased expressions of Bcl-2, p-ERK, and p-Akt and increased expressions of Bax, p-JNK, and p-p38 were observed in liver tissues of 5-FU and IGBR group in comparison to those of the model group.
Conclusion IGBR can regulate Bax and Bcl-2 through MAPK and PI3K/Akt signaling pathway and induce cell apoptosis of liver cancer caused by DEN exposure in rats.
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