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只倚瘤裸鼠分为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及顺铂均町抑制移植瘤的生长,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.

abstractsObjective 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 MTT 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 A549.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 A549 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 ＜ 0.01).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.