草苁蓉环烯醚萜苷对肝癌抑制作用

崔香丹; 郑峰; 朱洁波; 全吉淑; 尹学哲

doi:10.11847/zgggws1117089

草苁蓉环烯醚萜苷对肝癌抑制作用

Inhibitive effect of iridoid glycosides from Boschniakia rossica on apoptosis of liver cancer cells

摘要

摘要:
目的探讨草苁蓉环烯醚萜苷（IGBR）对二乙基亚硝胺（DEN）诱发大鼠肝癌细胞凋亡的影响及其可能作用机制。
方法 Wistar雄性大鼠随机分为对照组和模型组、5–氟尿嘧啶（5-FU）组、IGBR组，除对照组外，其余大鼠第1天给予腹腔注射DEN 200 mg/kg 1次，自由饮用0.05 %的DEN水溶液；5-FU组大鼠腹腔注射25 mg/kg 5-FU，每周3 次；IGBR组大鼠灌胃500 mg/kg IGBR每日1次。实验第12、20、28周末分批处死动物，TUNEL法检测肝细胞凋亡，Western blot法检测肝组织中Bax、Bcl-2和丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3激酶/蛋白激酶B（PI3K/Akt）通路相关蛋白表达。
结果与对照组比较，模型组大鼠肝细胞凋亡指数（12.3 ± 0.4）%明显升高；与模型组比较，5-FU组与IGBR组大鼠肝细胞凋亡指数分别为（22.3 ± 0.2） %、（22.2 ± 0.1） %明显升高（P < 0.05），5-FU组与IGBR组之间差异无统计学意义（P > 0.05）。与对照组比较，模型组大鼠肝组织中p-ERK、p-Akt表达水平下降、p-JNK、p-p38表达水平升高，ERK、p38、JNK、Akt表达无显明变化；与模型组比较，5-FU组与IGBR组大鼠肝组织中Bcl-2和p-ERK、p-Akt表达水平下降，Bax和p-JNK、p-p38表达水平升高。
结论 IGBR可通过MAPK、PI3K/Akt信号通路，调节Bax和Bcl-2表达，诱发DEN大鼠肝癌细胞凋亡。

Abstract:
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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