Xing Lihua, Zhang Zhenxiang, Xu Yongjian, Zhang Huilan, Liu Jianbo
Research Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R.China.
Zhongguo Fei Ai Za Zhi. 2004 Jun 20;7(3):191-5. doi: 10.3779/j.issn.1009-3419.2004.03.02.
To study the effect and possible mechanism of cyclooxygenase-2 selective inhibitor, nimesulide (NIM), combined with cisplatin (DDP) on human lung cancer.
The proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT reduction assay and flow cytometry respectively. The inhibitory effects of NIM and DDP to neoplasia were verified on subcutaneous implanted tumor of nude mice.
Both NIM and DDP could inhibit A549 cell proliferation in a concentration dependent pattern. When NIM (25 μmol/L) and DDP (≥1 mg/L) were combined, the inhibitory effect was enhanced in a synergistic or additive pattern. Both NIM (25 μmol/L) and DDP (3 mg/L) could significantly increase the apoptosis of A549 cells ( P < 0.05, P < 0.01), and this action was remarkably increased when DDP was combined with NIM ( P < 0.01, P < 0.01). NIM and DDP could inhibit the growth of subcutaneous implanted tumor on nude mice and the inhibitory rate of NIM combined with DDP was significantly higher than that of NIM or DDP alone ( P < 0.01, P < 0.01).
NIM combined with DDP shows significantly synergistic anti-tumor effects on lung cancer cell line A549 and subcutaneous implanted tumor on nude mice, which may be achieved by enhancement of growth inhibition and apoptosis induction to tumor cells.
研究环氧化酶-2选择性抑制剂尼美舒利(NIM)联合顺铂(DDP)对人肺癌的作用及可能机制。
分别采用MTT比色法和流式细胞术评估人肺癌细胞系A549的增殖和凋亡情况。通过裸鼠皮下移植瘤验证NIM和DDP对肿瘤形成的抑制作用。
NIM和DDP均可呈浓度依赖性抑制A549细胞增殖。当NIM(25μmol/L)与DDP(≥1mg/L)联合时,抑制作用呈协同或相加增强。NIM(25μmol/L)和DDP(3mg/L)均可显著增加A549细胞凋亡(P<0.05,P<0.01),DDP与NIM联合时该作用显著增强(P<0.01,P<0.01)。NIM和DDP均可抑制裸鼠皮下移植瘤生长,NIM联合DDP的抑制率显著高于NIM或DDP单独使用时(P<0.01,P<0.01)。
NIM联合DDP对肺癌细胞系A549及裸鼠皮下移植瘤具有显著的协同抗肿瘤作用,可能是通过增强对肿瘤细胞的生长抑制和凋亡诱导实现的。