关键词: 肺肿瘤, 顺铂, 抗药性, 肿瘤

Abstract: Objective To establish a nude mouse model of cisplatin-resistant lung cancer and to evaluate the modeling effect. 
Methods Human lung adenocarcinoma A549 cells and human lung adenocarcinoma cisplatin-resistant A549 cells (A549/DDP) were cultured in vitro, and cell suspensions were inoculated subcutaneously on the back of nude mice to construct a tumor-bearing nude mouse model of lung cancer. Tumor cells were separated and primary culture was performed. Cisplatin solution was selected as the experimental drug, and 10 groups were set up according to concentration gradients (0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, and 64 mg/L) to intervene in A549 and A549/DD P cells, respectively. MTT assay was used to detect OD values at three time points (24 h, 48 h, and 72 h), to calculate cell inhibition rate. The half maximal inhibitory concentration (IC50) of cisplatin was obtained, to determine the multiples of drug resistance, and to verify whether the lung cancer model had cisplatin resistance properties. 
Results ① With the increase of time and concentration, the inhibition rate of cisplatin on A549/DDP cells gradually increased, showing significant difference of interaction between groups, time points and time points between groups (P＜0.05). ②With the increase of time and concentration, the inhibition rate of cisplatin on A549 cells gradually increased, showing significant difference of interaction between groups and between time points (P＜0.05); there was an interaction between groups and time points (P＜0.05). ③At the same time and concentration, the inhibitory rate of cisplatin on A549 cells was significantly higher than that on A549/DDP cells, showing significant difference between groups (P＜0.05). ④With the increase of time, the IC50 of cisplatin on A549 and A549/DDP cells gradually decreased, showing significant difference of interaction between groups and between time points (P＜0.05); there was an interaction between groups and time points (P＜0.05). ⑤The multiples of drug resistance obtained after intervention for 24 h, 48 h, and 72 h were 12.395±1.209, 29.043±2.178, and 16.902±0.727, respectively; There was a significant difference between the groups (P＜0.05). All indicated a high degree of drug resistance of cells, with the optimal resistance observed at 48 h. 
Conclusion A nude mouse model of cisplatin-resistant lung cancer can be successfully constructed by subcutaneous inoculation of A549/DDP cell suspension. This model can provide a good carrier for further studying the biological mechanisms of occurrence and evolution of drug resistance. 

Key words: lung neoplasms, cisplatin, drug resistance, neoplasm