摘要
目的 探讨环氧化酶 2 (COX 2 )抑制剂尼米舒利 (NIM )与化疗药顺铂 (DDP)联合应用治疗肺癌的效应及可能机制。方法 应用MTT试验及流式细胞术分别检测NIM与DDP联用对人肺腺癌A5 49细胞增殖和凋亡的影响 ,裸鼠移植瘤实验检测NIM与DDP联用对A5 49细胞成瘤性的影响。结果 在一定浓度范围内NIM、DDP均可抑制A5 49细胞的生长 ,其抑制作用呈量 效关系。NIM ( 2 5 μmol/L)与DDP合用可增强对A5 49细胞生长的抑制作用 ,DDP浓度≥ 1mg/L时二者有协同或相加作用。NIM及DDP可有效诱导A5 49细胞凋亡 ,联用后凋亡率显著增加。裸鼠移植瘤体内实验显示NIM与DDP均可抑制移植瘤生长 ,联用后抑瘤率显著增高。结论 NIM与DDP联用对A5 49细胞、肺癌移植瘤有显著的协同抗肿瘤效应 ,该作用可能是通过增强对A5
Objective To study the effect and possible mechanism of cyclooxygenase 2 selective inhibitor, nimesulide (NIM), combined with cisplatin (DDP) on human lung cancer. Methods 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. Results 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). Conclusion 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.
出处
《中国肺癌杂志》
CAS
2004年第3期191-195,共5页
Chinese Journal of Lung Cancer
关键词
肺肿瘤
凋亡
环氧化酶-2
顺铂
Lung neoplasms Apoptosis Cyclooxygenase-2 Cisplatin