尼美舒利联合顺铂对A549肺腺癌细胞裸鼠移植瘤免疫功能的影响

Effect of nimesulide combined with ciplatin on immunological function in nude mouse with transplantation tumor of lung adenocarcinoma cells line A549

目的 探讨尼美舒利联合顺铂对A549肺腺癌细胞裸鼠移植瘤免疫功能的影响.方法 选择无特定病原体级BALB/C裸鼠32只,完全随机分为对照组、尼美舒利组、顺铂组和尼美舒利联合顺铂组（联合组）,每组8只.取对数生长期的肺腺癌A549细胞接种于32只裸鼠背部皮下组织,0.2 ml/只,构建肺腺癌裸鼠移植瘤模型.细胞接种后8d,对照组给予羟甲基纤维素钠溶液10 ml/（kg·d）灌胃,连续给药21 d和腹腔注射0.9％氯化钠溶液,0.5 ml/次,1次/4d,共4次.尼美舒利组给予尼美舒利灌胃,60 mg/（kg·d）,连续给药21 d.顺铂组给予顺铂腹腔注射,5 mg/kg,1次/4d,共4次.联合组给予尼美舒利60 mg/（kg·d）灌胃＋顺铂5 mg/kg腹腔注射.酶联免疫吸附试验测定不同用药组瘤组织中白细胞介素10（IL-10）、IL-12及肿瘤坏死因子α（TNF-α）表达情况.结果 接种肺腺癌A549细胞后,对照组、顺铂组、联合组裸鼠各死亡1只,尼美舒利组死亡2只,其余均在细胞接种后的8～10d瘤体逐渐增大,成瘤率84.4％（27/32）.尼美舒利组、顺铂组及联合组IL-10含量均明显低于对照组[（30.47±1.61）、（26.45±1.39）、（20.59±1.67） ng/L比（44.97 ±9.47） ng/L],联合组明显低于顺铂组和尼美舒利组,差异均有统计学意义（均P ＜0.05）.尼美舒利组、顺铂组及联合组IL-12、TNF-α含量均明显高于对照组[IL-12：（0.53±0.10）、（1.05 ±0.27）、（1.89±0.61） ng/L比（0.24 ±0.21） ng/L,TNF-α：（7.2±1.4）、（11.6±2.9）、（109.4 ±65.3） μg/L比（3.3±1.4） μg/L],联合组明显高于顺铂组及尼美舒利组,差异均有统计学意义（均P＜0.05）.结论 在增强移植瘤裸鼠免疫功能方面,尼美舒利和顺铂联合用药效果优于单一用药;与增加裸鼠移植瘤IL-12和TNF-α含量、抑制IL-10含量有关.

Objective To explore the effect of nimesulide combined with ciplatin on immunological function in lung adenocarcinoma cells line A549.Methods Totally 32 BALB/C rats were randomly divided into control group,nimesulide group,cisplatinon group and nimesulide combined with cisplatinon （combination） group （n =8 in each group）.The lung adenocarcinoma A549 cells of logarithmic phase （0.2 ml） were inoculated subcutaneously on the mice back to construct nude mouse transplantation lung tumor model.Eight days after inoculation,intragastric administration of hydroxymethyl cellulose sodium solution [10 ml/（kg · d）,21 d] and intraperitoneal injection of 0.9% sodium chloride solution （0.5 ml/time,1 time/4 days,totally 4 times） were given in control group;intragastric administration of nimesulide [60 mg/（kg · d）,21 days] was given in nimesulide group;intraperitoneal injection of cisplatin [5 mg/kg,1 time/4 days,totally 4 times] was given in cisplatin group;intragastric administration of nimesulide and intraperitoneal injection of cisplatin were given in combination group.Enzyme-linked immunosorbent assay was used to determine the expressions of interleukin （IL）-10,IL-12 and tumor necrosis factor-α （TNF-α）.Results After inoculation of lung adenocarcinoma A549 cells,1 animal died in control group,one died in cisplatin group and one died in combination group.2 animals died in nimesulide group;the tumors volume increased gradually 8-10 d after inoculation in animals,showing a tumorigenecity of 84.4% （27/32）.The levels of IL-10 in nimesulide group,cisplatin group and combination group were significantly lower than those in control group[（30.47 ± 1.61）,（26.45 ± 1.39）,（20.59 ± 1.67） ng/L vs （44.97 ± 9.47） ng/L],and they were significantly lower in combination group than those in cisplatin group and nimesulide group （P 〈 0.05）.The levels of IL-12 and TNF-α in nimesulide group,cisplatin group and combination group were significantly higher than those in control group[（0.53 ±0.10）,（1.05 ±0.27）,（1.89 ±0.61） ng/L vs （0.24±0.21） ng/L;（7.2±1.4）,（11.6 ±2.9）,（109.4 ±65.3） μg/L vs （3.3 ± 1.4） μg/L],and they were significantly higher in combination group than those in cisplatin group and nimesulide group （P 〈 0.05）.Conclusion Nimesulide combined with cisplatin can effectively increase the levels of IL-12 and TNF-α and reduce the level of IL-10,thus to improue the immunological function,and combination therapy is superior to single drug application.