Ginsenoside Compound K Induced Implanted Hepatoma Tumor Apoptosis In Nude Mice By Erssignal Pathway

Objective:To investigate the effect of ginsenoside Compound K(20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol;CK)on the apoptosis of human hepatocarcinoma SMMC-7721 cells in nude mice and the mechanism of endoplasmic reticulum stress.Methods:The BALB/c nude mice bearing human HCC xenografts were randomized to groups that received CK(5,10,or 20 mg/kg)，5-Fu or normal saline(Vehicle)every day for 15 day.The weight and volume of the HCC xenografts were measured by caliper,and the growth inhibition rate was calculated;Morphological changes of HCC xenografts cells were observed by HE staining;Apoptosis of HCC xenografts cells were detected by TUNEL after ginsenoside CK and 5-Fu treatment;At last,endoplasmic reticulum stress-related proteins GRP78,p-eIF2α,p-JNK,Caspase4 and CHOP were detected by Western blot.Results:1.Antitumor activity of CK in nude mice showed:With the increasing concentration of ginsenoside CK,compared with vehicle controls,tumor weights and volumes were significantly reduced.The tumor inhibition rates were 38.64%,44.01%,51.79%and 60.89%for 5,10,20 mg/kg CK and 5-Fu,respectively.Additionally,there were no significant differences in body weight among the vehicle and 5 and 10 mg/kg CK-treated groups.2.HE staining assay showed:the HCC xenografts cells of the nude mice in the vehicle group were intact with some atypia.And it was not significantly necrotic of the tumor tissue in vehicle group.After ginsenoside CK and 5-Fu treatment,cell nucleus were pyknosis and fragmentation.Necrotic cells in the tumor tissues were significantly increased.TUNEL staining assay showed:The nuclei were stained blue and purple by hematoxylin in vehicle group.However,the positive apoptosis cells were obviously increased in ginsenoside CK and 5-Fu group by TUNEL staining.3.Western blot results showed:The expression of GRP78、p-eIF2a、p-JNK、Active-caspase4 and CHOP were increased with ginsenoside CK treatment.Conclusion:Taken together,our results showed that ginsenoside CK inhibited tumor growth and induced cells apoptosis.The main mechanism are related to endoplasmic reticulum stress pathway.