The function and mechanism of astragaloside Ⅳ on the chemoresistance of HepG2/GCs cell lines
	    		
		   		
		   			
		   		
	    	
    	 
    	10.3760/cma.j.issn.1007-8118.2018.08.014
   		
        
        	
        		- VernacularTitle:黄芪甲苷逆转人肝癌HepG2/GCS细胞多药耐药的作用及其机制
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Yanzhang TIAN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Fei GAO
			        		
			        		;
		        		
		        		
		        		
			        		Haichao ZHAO
			        		
			        		;
		        		
		        		
		        		
			        		Haoliang ZHAO
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 山西医学科学院山西大医院普通外科
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Carcinoma,heoatocytes;
			        		
			        		
			        		
				        		Multidrug resistance;
			        		
			        		
			        		
				        		Astragaloside Ⅳ;
			        		
			        		
			        		
				        		Adriamycin
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Chinese Journal of Hepatobiliary Surgery
	            		
	            		 2018;24(8):555-559
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	Objective To investigate whether astragaloside Ⅳ can regulate the multidrug resistance of HepG2/GCS-resistant cell lines,restore the sensitivity of drag-resistant cell lines to adriamycin (ADM) and its mechanism.Methods We used recombinant GCS (shRNAS) and control recombinant plasmids and did the transfection with HepG2 cells.RT-PCR and Western blot were used to analyze the expression of GCS.Astragaloside Ⅳ cytotoxicity experiments and ADM were performed in experimental and control groups.Hoechst 33258 was detected in two groups,apoptosis was detected by flow cytometry,and protein expression of caspase 9,3,Bax,and bcl-2 were detected by Western blot.Results RT-PCR and fluorescence observation showed that GCS was highly expressed after the transfection.Western blot showed that compared with control group,and HepG2GCS group,GCS and MDR1 expression were higher than;Astragaloside Ⅳ cytotoxicity experiment showed tumor proliferation was not regulated by GCS(FHepG2GCS=0.308,FHepG2EV =0.216,FHepG2 =0.153,P> 0.05),ADM in vitro tumor cell inhibition experiments showed that HepG2GCS cells were resistant to ADM (50% cell transplantation concentration were 7.5,7.5,15 μg/ml);Hoechst 33258 and flow cytometry showed that Astragaloside Ⅳ can restore ADM tumor inhibition;Western blot showed that compared to untreated HepG2EV and HepG2GCS cells,protein level of caspase 9,caspase 3 were increased in Ast+HepG2EV and Ast+HepG2GCS groups (t=7.17,P<0.05).At the same time,Bax and Bcl-2 were significantly different in each group (P< 0.05).Conclusions Astragaloside Ⅳ reverses multidrug resistance in HepG2/GCS cell lines,restores its sensitivity to ADM,promotes apoptosis in tumor cells through the caspase pathway and Bax pathway,and thus plays an important role in cancer chemotherapy.