Effect and mechanism of nimesulide combined with cisplatin on proliferation and apoptosis of lung cancer

Abstract

Objective To evaluate the effects of selective cyclooxygenase-2 inhibitor nimesulide lone and combined with cisplatin on tumor growth,and Ki67 and Caspase-3 expression in lung cancer xenografts in nude mice. Methods The mice were randomly divided into 4 groups:the control group,the nimesulide group,the cisplatin group and the nimesulide combined with cisplatin group. A549 cells were injected into BALB/c nude mice subcutaneously.On the 21st day after treatment tumor tissues were collected,and the xenografts growth were observed. The expression of Ki67 and Caspase-3 were detected by immunohistochemical method.Results Nimesulide combined with cisplatin could significantly inhibited the xenografts growth compared with nimesulide or cisplatin.The tumor inhibition rate was 44.33％ in the nimesulide group,53.61％ in the cisplatin group and 80.41％ in the nimesulide combined with cisplatin group (P ＜ 0.05).Immunohistochemical analysis showed that the expression rates of Caspase-3 was significantly increased in the nimesulide combined with cisplatin group (67.43 ± 23.57 ) ％,the cisplatin group (48.40 ± 20.37 ) ％,and the nimesulide group (38.65 ± 15.37)％,compared with the control group (27.63 ± 13.03)％ (P ＜ 0.05).The expression rate of Caspase-3 was significantly increased in the nimesulide combined with cisplatin group compared with the nimesulide group or the cisplatin group (P ＜ 0.05 ).The expression rate of Ki67 was significantly decreased in the nimesulide group combined with cisplatin group (24.34 ± 15.90)％,the cisplatin group (40.85 ± 22.47)％ and the nimesulide group (53.33 ± 19.67)％ compared with the control group ( 80.43 ± 16.88 ) ％ ( P ＜ 0.05 ).The expression of Ki67 was significantly decreased in the nimesulide combined with cisplatin group compared with the nimesulide group or the cisplatin group ( P ＜ 0.05 ).Conclusion Nimesulide can inhibit human lung cancer A549 cells xenografts in nude mice growth,Nimesulide enhanced the inhibitory effects of cisplatin.The mechanism may be related to inhibition of tumor cell Ki-67 expression,increased expression of Caspase-3,inhibition of tumor cell proliferation,and inducing tumor cell apoptosis. Key words: Lung neoplasms ; Cisplatin ; Cell proliferation ; Apoptosis ; Nimesulide