| Objective:To investigate the mechanism of Ginsenoside compound K inhibiting the growth of primary hepatocellular carcinoma in rats and its endoplasmic reticulum stress.The model of primary liver cancer in rats was established by intermittent administration of diethylenenitrosamine(DEN).Method:54 male SD rats were selected and randomly divided into a blank control group(9 rats)and an experimental group(45 rats).DEN intermittent administration was used to establish a model of primary liver cancer in rats.The experimental group was given 0.01%DEN solution to drink freely for 5 w.At the beginning of week 6,the rats were free to drink sterile water for 2 w,From week 8,the rats were given 0.01%DEN solution to drink freely for 6 w.From week 14,the rats were free to drink sterile water again for 3 w.At the end of week 16,rats in the experimental group received PET-CT to detect tumor changes in the liver region of rats and calculate the maximal standardized uptake value(SUV).At the beginning of week 17,experimental group rats were randomly divided into model group,low,medium and high doseGinsenoside compound K group and positive control group,9 rats in each group.Rats in the low,medium and high dose groups of Ginsenoside compound K were injected with Ginsenoside compound K(2.5 mg/kg,5 mg/kg,10 mg/kg),while 5-Fu(5 mg/kg)was injected into the positive control group,and normal saline of the same volume was injected into the control group and model group once a day for 2 w.At the end of the 18th week,the rats in the experimental group underwent pet-ct again to detect the tumor changes in the liver region of the rats and calculate the SUV value.Morphological changes of rat liver were detected by HE staining.TUNEL staining was used to detect the apoptosis of rat liver cells.Western Blot was used to detect the expressions of ERS related proteins GRP78,p-elf2α,p-JNK,CHOP,Cleaved caspase-12,and apoptotic protein Cleaved caspase-3 in rat liver cancer.Results:1.During the experiment,it was found that the rats in the model group had changes such as listlessness,lack of food and rat hair dullness.After anatomy,it was found that the liver was swollen,the edges were bumpy,and there were grayish-white nodules of different sizes on the surface and bleeding spots were visible.The above symptoms were improved in the experimental group and the positive control group.2.PET-CT results showed tumor areas appeared in the liver tissue of rats before administration.Compared with that before administration,after Ginsenoside compound K administration,tumor areas in rat liver tissue decreased.SUV value of rat liver tissue after administration was significantly different from that before administration(P<0.05 or P<0.01).3.HE staining results showed that the hepatocytes of the model group showed heteromorphic changes and the hepatic plates fused into groups.Inflammatory cell invasion occurred in low,medium and high dose groups of Ginsenoside compound K,and the number of necrotic cells increased with the increase of Ginsenoside compound K dose the hepatocytes of the model group.4.TUNEL staining results showed that a small number of positively stained brown apoptotic cells were found in the model group,and the number of positively stained brown apoptotic cells was increased in the low,medium and high dose groups of ginsenoside CK.Compared with the model group,the low,medium and high dose groups of ginsenoside CK showed significant differences with statistical significance(P<0.05).5.Western blot staining results showed results showed that compared with the model group,the iexpression of RS related proteins GRP78,p-elf2α、p-JNK、CHOP、Cleaved caspase-12 and apoptotic protein Cleaved caspase-3 were significantly different afterGinsenoside compound K administration(p<0.05 or P<0.01).Conclusion:Ginsenoside compound K can inhibit the growth of primary liver cancer in rats,and its mechanism is related to the activation of endoplasmic reticulum stress response. |
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