蛋白激酶C抑制剂联合顺铂治疗非小细胞肺癌的实验研究  

Effects of a protein kinase C inhibitor combined with cisplatin on non-small cell lung cancer

作　　者：高志强[1] 韩宝惠[1] 沙慧芳[2] 史振余[2] 杨晓华[2] 冯久贤[2] 

机构地区：[1]上海交通大学附属胸科医院肺内科,200030 [2]上海交通大学基础研究室,200030

出　　处：《中华结核和呼吸杂志》2010年第4期284-288,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：基金项目：上海市科委科技发展基金资助项目（06DZ19501）;上海市胸科医院科技发展基金资助项目（Y209-05）

摘　　要：目的初步探讨蛋白激酶c（PKC）抑制剂白屈菜红碱（CH）与化疗药物顺铂联合应用在非小细胞肺癌（NSCLC）治疗中的作用及其可能的机制。方法应用四甲基偶氮唑蓝试验及流式细胞术分别检测CH、顺铂以及CH与顺铂联用对人NSCLC细胞株A549增殖和凋亡的影响。用裸鼠移植瘤实验检测CH、顺铂以及CH与顺铂联用对A549细胞成瘤性的影响。应用人肺腺癌细胞株A549细胞构建裸鼠皮下移植瘤模型，用随机数字表法将24只荷瘤裸鼠分为CH组、顺铂组、CH＋顺铂组及生理盐水对照组，每组5只，裸鼠分别腹腔注射CH、顺铂、CH＋顺铂和生理盐水（共3周，顺铂及生理盐水每周注射1次，CH每周注射2次），观察移植瘤的生长情况。结果CH可抑制NSCLC细胞株A549增殖，浓度增加其细胞毒作用亦增强，CH与顺铂联用呈协同或相加作用；CH组、顺铂组及CH＋顺铂组A549细胞的凋亡率分别为（5．36±0．70）％、（5．23±0．55）％及（17．28±2．17）％，均高于对照组的（2．75±0．35）％（t=7．88，P〈0．05），CH＋顺铂组A549细胞的凋亡率分别高于CH组及顺铂组（t=5．62，P〈0．05）；裸鼠移植瘤体内实验结果表明，CH及顺铂均可抑制移植瘤的生长，CH＋顺铂组的抑瘤率（80．5％）高于CH组（72．4％）及顺铂（64．3％）组（t=11．34，P〈0．01）。结论CH与顺铂联用对A549细胞及裸鼠移植瘤有显著的协同抗肿瘤作用，其作用机制可能是通过增强对A549细胞增殖的抑制以及诱导其凋亡而实现。Objective To study the effects and possible mechanisms of the protein kinase C （PKC） inhibitor chelerythrine chloride （CH）, combined with cisplatin （DDP） on human non-small cell lung cancer. Methods The effect of CH, DDP and the combination on proliferation and apoptosis of human lung cancer cell line A549 were evaluated by M3W assay and flow cytometry respectively. The inhibitory effects of CH and DDP on neoplasia were verified on subcutaneous implanted tumor of nude mice. Implanted tumor models were constructed in nude mice using human lung adenocarcinoma cell line 3-549. Twenty-four BALB/ c nude mice with implanted tumors were divided into 4 groups randomly： group CH, group DDP, group CH ＋ DDP, and normal saline group （group NS）, each with 5 mice. CH, DDP or NS were intraperitoneally injected into nude mice for 3 weeks （DDP or NS was injected once a week, CH was injected twice a week）. Results CH inhibited A549 cell proliferation in a concentration-dependent pattern. When CH and DDP were combined, the inhibitory effect was enhanced in a synergistic or additive pattern. Both CH and DDP significantly increased the apoptosis of 3_549 cells, and this action was remarkably increased when DDP was combined with CH. CH and DDP inhibited the growth of subcutaneous implanted tumor in nude mice and the inhibitory rate of group CH ＋ DDP （80. 5% ） was significantly higher than that of group CH（72.4% ） or group DDP（64. 3% ） （ t = 11.34, P 〈 O. 01 ）. Conclusion CH combined with DDP shows significantly synergistic anti-tumor effects on non-small cell lung cancer cell line A549 and subcutaneous implanted tumor in nude mice, possibly by enhancement of growth inhibition and apoptosis induction on tumor cells.

关 键 词：癌 非小细胞肺 模型 动物 顺铂 白屈菜红碱 

分 类 号：R734.2[医药卫生—肿瘤]