多烯磷脂酰胆碱对奥沙利铂治疗人胃癌裸鼠模型效果影响及其机制

EFFECT OF POLYENE PHOSPHATIDYLCHOLINE TO OXALIPATIN THERAPY IN GASTRIC CARCINAOMA XENOGRAFTS IN NUDE MICE

目的探讨人胃癌裸鼠模型中不同剂量多烯磷脂酰胆碱(易善复)对奥沙利铂治疗效果的影响及其机制。方法将人胃癌细胞SGC-7901接种于裸鼠皮下,建立人胃癌裸鼠皮下移植瘤模型。随机分为6组:葡萄糖对照组、奥沙利铂组、易善复组及高、中、低剂量易善复联合奥沙利铂组。连续给药2周,停药24 h后处死裸鼠,称取瘤质量,计算抑瘤率,并检测用药后裸鼠的血常规及肝肾功能,检测瘤组织中超氧化物歧化酶(SOD)含量,流式细胞仪测定细胞周期,免疫组化法测定半胱氨酸天冬氨酸蛋白酶-3(caspase-3)、错配切除修复蛋白1(ERCC-1)和谷胱甘肽巯基转移酶(GST-π)的表达。结果与对照组比较,奥沙利铂有明显抑制肿瘤生长的作用,易善复不能抑制肿瘤生长,各剂量易善复联合奥沙利铂组可抑制肿瘤生长,但与奥沙利铂组比较抑瘤率低;各剂量易善复联合奥沙利铂组随易善复浓度升高,SOD水平升高,caspase-3、ERCC-1和GST-π的表达下降。结论易善复对奥沙利铂化疗疗效有拮抗作用,且呈剂量依赖性,可能与调节caspase-3、ERCC-1和GST-π表达有关。

Objective To explore the anti-tumor effect and machanism of polyene phosphatidylcholine with different concentrations with oxaliplatin on the growth of SGC-7901 cell subcutaneously implanted tumor in nude mice.MethodsA tumor model of human gastric carcinoma was created by subcutaneous inoculation of SGC-7901 cells into nude mice.The mice were randomized to glucose group,oxaliplatin group,polyene phosphatidylcholine group,high-,medium-,and low-dose polyene phosphatidylcholine with oxaliplatin groups.The mice in each group received intraperitoneal injection of the drugs for 2 weeks,and were sacrificed 24 hours after the last injection and tissue specimen was obtained.Tumor inhibition rate was calculated,detecting the contents of SOD,cell cycle detected with flow cytometry,the expression of caspase-3,ERCC-1 and GST-π was determined with immunohistochemistry method.ResultsCompared with control group,oxaliplatin significantly inhibited tumor growth in vivo,polyene phosphatidylcholine did not inhibit tumor growth,the groups of different concentrations of polyene phosphatidylcholine and oxaliplatin could inhibit tumor growth,but compared with the group of oxaliplatin tumor inhibition rate was lower,with the growth concentration of polyene phosphatidylcholine,the content of SOD was heightened,expression of caspase-3,ERCC-1,GST-π were decreased.ConclusionPolyene phosphatidylcholine was antagonistic on oxaliplatin,showing dose dependent,the mechanism may be related to the up-regulation of the activity of caspase-3,ERCC-1 and GST-x.