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Inhibitory effect of pristimerin on diethylnitrosamine⁃induced hepatocellular carcinoma in rats by regulating ROS/ASK1/JNK signal pathway
Received date: 2023-05-25
Online published: 2023-11-15
Objective To investigate the influence of pristimerin (Pris) on rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) by regulating ROS/ASK1/JNK signal pathway. Methods Six SD rats were randomly selected as the control group, and the remaining rats were injected with DEN to construct the rat model of HCC. The rats successfully modeled were randomly grouped into HCC group, Pris group (0.8 mg/kg Pris), Vaccarin group (100 mg/kg ROS/ASK1/JNK signal pathway inhibitor Vaccarin), and Pris+Vaccarin group (0.8 mg/kg Pris+100 mg/kg Vaccarin), with 6 rats in each group, and were injected continuously for one week. HCC group and control group were injected with the same amount of normal saline. Body weight, liver weight and liver weight ratio were measured; liver function, inflammatory factors, antioxidant index and ROS level were detected by ELISA; HE staining was applied to detect the pathological changes of liver; western blot was applied to detect the expression of apoptotic markers (Bax, Bcl-2 and cleaved-Caspase-3) and ROS/ASK1/JNK signal pathway protein. Results The rats in the control group showed normal liver tissue structure. In HCC group, necrosis of some hepatocytes and focal nodular hyperplasia were observed, body weight, Bax, cleaved-Caspase-3, ROS, p-ASK1/ASK1, and p-JNK/JNK level in HCC group were obviously lower than those in the control group (P < 0.05), but liver weight, liver weight ratio, ALT, AST, ALP, LDH contents, IL-6, TNF-α, CCL-2 contents, SOD, GR, GPx, CAT contents, and Bcl-2 protein level were obviously higher (P < 0.05). Hepatocyte necrosis and focal nodular hyperplasia in Pris group were improved, and body weight, Bax, cleaved-Caspase-3, ROS, p-ASK1/ASK1, and p-JNK/JNK level in Pris group were obviously higher than those in HCC group (P<0.05); liver weight, liver weight ratio, ALT, AST, ALP, LDH contents, IL-6, TNF-α, CCL-2 contents, SOD, GR, GPx, CAT contents, and Bcl-2 protein level were obviously lower (P<0.05). The opposite trend was observed in Vaccarin group; Vaccarin reversed the anticancer effect of Pris on HCC rats. Conclusion Pris may play a certain role in inhibiting HCC rats by activating ROS/ASK1/JNK signal pathway.
Yan LIU , Donghua ZHANG , Yuqian HUANG , Youshun LIU , Ji. HUANG . Inhibitory effect of pristimerin on diethylnitrosamine⁃induced hepatocellular carcinoma in rats by regulating ROS/ASK1/JNK signal pathway[J]. The Journal of Practical Medicine, 2023 , 39(20) : 2597 -2602 . DOI: 10.3969/j.issn.1006-5725.2023.20.007
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