Triptolide increases the radiosensitivity of lung cancer cells by inhibiting DNA repair and inducing apoptosis
	    		
		   		
		   			
		   		
	    	
    	 
    	10.3760/cma.j.cn112152-20191212-00800
   		
        
        	
        		- VernacularTitle:雷公藤甲素抑制DNA修复诱导细胞凋亡增加肺癌细胞放射敏感性
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Rongqin DAI
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Haibo WANG
			        		
			        		;
		        		
		        		
		        		
			        		Weiqing LIU
			        		
			        		;
		        		
		        		
		        		
			        		Linwei LI
			        		
			        		;
		        		
		        		
		        		
			        		Wei WANG
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 河南省人民医院中心重症医学科,郑州大学人民医院 450003
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Lung neoplasms;
			        		
			        		
			        		
				        		Triptolide;
			        		
			        		
			        		
				        		Radiosensitivity;
			        		
			        		
			        		
				        		DNA repair;
			        		
			        		
			        		
				        		Apoptosis
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Chinese Journal of Oncology
	            		
	            		 2021;43(12):1235-1240
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
            	- 
		        	Abstract:
			       	
			       		
				        
				        	Objective:To investigate the effect of triptolide on radiosensitivity of lung cancer cells and its mechanism.Methods:The lung cancer cells H1299, A549, H157 and H838 were cultured. The strongest radio resistance cell line, H1299 was selected by cell clone formation experiment and for the subsequent experiments. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) was used to detect the effect of different concentrations of triptolide on the proliferation of H1299 cells. The optimal concentration of triptolide was 50nmol/L, and the optimal treatment time was 48 hours. The H1299 cells were divided into the control group, triptolide group (50 nmol/L), 4 Gy group and triptolide+ 4 Gy group. Flow cytometry was used to detect the apoptosis rate of H1299 cell. Western Blot was used to detect the proteins expression levels of p-Chk2, p-ATM, p-p53, Bcl-2, Bax and cleaved-Caspase 3.Results:The apoptotic rate and protein levels of Bax, cleaved-Caspase 3, p-Chk2, p-ATM and p-p53 in the 4 Gy group were (12.38±1.34)%, 0.42±0.04, 0.38±0.04, 0.98±0.11, 0.73±0.08, 0.95±0.09, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03, 0.32±0.03, 0.21±0.02, 0.25±0.03 in the control group ( P<0.05). However, the protein level of Bcl-2 was (0.52±0.05), lower than (0.93±0.09) of the control group ( P<0.05). The survival fraction (0.462) and protein level of Bcl-2 (0.44±0.04) in the triptolide group were lower than those of the control group (0.702 and 0.93±0.09, P<0.05). The apoptotic rate and the protein levels of Bax and cleaved-Caspase 3 in the triptolide group were (9.27±1.08)%, 0.45±0.05, 0.41±0.04, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03 in the control group ( P<0.05), and the sensitization ratio in the triptolide group was 1.579. The apoptosis rate, Bax and cleaved Caspase 3 protein expression levels in triptolide + 4 Gy group were (26.53±2.19)%, 0.91±0.09 and 0.79±0.08, respectively, higher than (12.38±1.34)%, 0.42±0.04 and 0.38±0.04 in 4 Gy group ( P<0.05). The expression level of Bcl-2 protein was (0.21±0.02), lower than (0.52±0.05) in 4 Gy group ( P<0.05). Conclusion:Triptolide increases the radiosensitivity of radiation-induced lung cancer cells by inhibiting DNA repair and inducing apoptosis.