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Objective:To investigate the effect of different chemotherapy drugs combined with DNA methylase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) on the apoptosis of lung adenocarcinoma cells.Methods:In the prospective randomized controlled study, lung adenocarcinoma A549 cells were treated with cisplatin plus paclitaxel (TP) or gemcitabine (GP) with or without 5-Aza-dC. According to different drug intervention methods, they were divided into control group, cisplatin combined with paclitaxel (TP) group, cisplatin combined with gemcitabine (GP) group, and 5-Aza-dC combined with TP group, 5-Aza-dC combined with GP group. CCK-8 assay was used to detect the proliferation of A549 cells. Transwell migration and invasion assay were used to detect the effect that each group of drugs on the migration and invasion ability of A549 cells. Quantitative Real-time Polymerase Chain Reaction was used to evaluate the effect of each treatment on the expression of apoptotic genes. One-way analysis of variance was used to compare the degree of cell proliferation in different drug treatment groups, and LSD- t method was used for pairwise comparison within groups. Results:The inhibition rates of lung adenocarcinoma cells in the TP regimen at different time points at 24, 48, and 72 h were as follows (20.00±4.23) %, (35.00±2.80) %, and (56.00±3.11) %. The inhibition rate of 5-Aza-dC combined with TP regimen on lung adenocarcinoma cells was significantly increased, at different time points of 24, 48 and 72 h, respectively (38.00±3.80) %, (50.00±3.25) %, (93.00±4.33) %. The inhibition rates of cells at different time points at 24, 48, and 72 h in the GP regimen were (33.00±5.10) %, (54.00±3.80) %, and (74.00±2.82) %, respectively; while 5-Aza-dC combined with GP regimen could significantly reduce the rate of cell growth, the inhibition rates of cells at 24, 48, and 72 h different time points were as follows (54.00±3.00) %, (67.00±5.30) %, and (95.00±1.13) %. The inhibitory effect of the same drug on lung adenocarcinoma cells increased with time (TP group: F=35.93, P<0.001; 5-Aza-dC combined with TP group: F=97.33, P<0.001; GP group: F =41.73, P<0.001; 5-Aza-dC combined with GP group: F=79.00, P<0.001), and at different time points, the differences were statistically different (all P<0.05). 5-Aza-dC combined with TP and GP chemotherapy regimens can inhibit the migration and invasion of lung adenocarcinoma cell A549, and the inhibitory effect is stronger than that of TP or GP regimens alone. The expression of Caspase 8 was significantly elevated ( t=5.87, P=0.004) in cells treated with 5-Aza-dC combined with GP when compared with GP regimen alone. The expression of Caspase 8 ( t=3.94, P=0.017), Caspase 6 ( t=5.81, P=0.004) and BBC3 (BCL-2 binding component 3) ( t=6.53, P=0.003) were increased when drugged with 5-Aza-dC combined TP regimen compared with TP regimen alone. Conclusion:5-Aza-dC might serve as a chemotherapeutic sensitizer to increase the sensitivity of lung adenocarcinoma cells.
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Objective@#This study aimed to investigate the relationship between the genetic variation of CD55 promoter and the risk of esophageal cancer.@*Methods@#A total of 700 esophageal cancer patients recruited between April 2008 and December 2012 at Tangshan Grongren Hospital and Tangshan Renmin Hospital, and 700 frequency matched controls were randomly selected from a pool of cancer free subjects recruited from a nutritional survey. Genotypes of CD55 rs2564978 polymorphism among all subjects were conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The OR and 95%CI were calculated by non-conditional Logistic regression to evaluate the association of CD55 rs2564978T/C polymorphism with the risk of esophageal cancer.@*Results@#The average age of cases and control was (60.04±9.19) and (59.21±9.98) years old. Compared with CD55 rs2564978 TT carriers, the individuals with CC genotype had a significantly higher risk of esophageal cancer (OR=1.94, 95%CI:1.42-2.66) . When stratified by sex, this genetic variation affected the risk of esophageal cancer among both males (OR=1.92, 95%CI:1.37-2.70) and females (OR=2.34, 95%CI:1.04-5.27). When stratified by age, the CD55 rs2564978 CC was associated with the susceptibility of developing esophageal cancer among younger individuals (OR=1.79, 95%CI:1.19-2.68) and older people (OR=2.32, 95%CI:1.41-3.83).When stratified by drinking status, CC genotype carriers increase the risk of esophageal cancer when drinking (OR=1.93, 95%CI:1.03-3.63) or not drinking (OR=1.95, 95%CI:1.36-2.80). When stratified by smoking status, CC genotype was associated with the risk of esophageal cancer among non-smokers (OR=1.79, 95%CI: 1.13-2.83), light smokers (less than 30 packs/year, OR=1.86, 95%CI:1.31-2.64) and heavy smokers (more than 30 packs/year, OR=2.67, 95%CI:1.28-5.57). Gene-environmental interaction analysis showed that CD55 rs2564978T/C polymorphism interacted with smoking status to increase the risk of esophageal cancer.@*Conclusion@#CD55 rs2564978 polymorphism effects on the risk of esophageal cancer.