益气养阴方影响Lewis肺癌移植小鼠肿瘤生长与调节Notch信号表达的关系

Relationship Between Effect of Yiqi Yangyin Decoction on Supressing Tumor-Bearing Lewis Lung Cancer Mice and Regulating Notch Signal Pathway

目的:通过不同剂量益气养阴方对Lewis肺癌移植小鼠肿瘤生长及肿瘤组织中Notch信号表达影响的观察,从调节Notch信号表达角度,探讨益气养阴方抑制肺癌生长的机制。方法:将60只荷瘤(Lewis肺癌细胞)近交系C57BL/6纯系小鼠随机分为4组:模型组、益气养阴方等效剂量组、益气养阴大剂量组、CTX化疗组,每组15只,模型组只行造模,益气养阴等效剂量组以小鼠体质量每克0.435 m L/g生药灌胃给药,3次/d,大剂量组按小鼠体质量1.36 m L/g生药灌胃给药,3次/d;CTX组按照20 mg/kg溶于0.2 m L生理盐水中腹腔注射,每周1次;各组均常规喂食;干预30 d后,观察记录各组肿瘤及Notch信号表达变化。结果:(1)肿瘤相对体积(RTV)及肿瘤相对抑制率:模型组肿瘤相对体积(RTV)为15.00±1.72,CTX组肿瘤相对体积(RTV)及相对肿瘤体积抑制率分别为8.86±0.91、40.92%,益气养阴等效剂量组肿瘤相对体积(RTV)及相对肿瘤体积抑制率分别为11.33±2.34、24.47%,益气养阴大剂量组为5.89±1.56、60.74%,上述3组较模型组RTV值均缩小(P<0.01),大剂量组RTV均低于其他3组(P<0.01),而CTX组肿瘤相对体积低于等效剂量组(P<0.05);肿瘤抑制率大剂量组较等效剂量组及CTX组高(P<0.05)。(2)肿瘤组织中Notch信号通路表达:模型组Notch1mRNA表达为1.03±0.27,Notch3mRNA表达为1.06±0.33,Jagged1mRNA表达为1.07±0.04,HeslmRNA表达为1.01±0.07;CTX组Notch1mRNA表达为0.24±0.05,Notch3mRNA表达为0.43±0.22,Jagged1mRNA表达为0.29±0.07,HeslmRNA表达为0.40±0.10;益气养阴等效剂量组Notch1mRNA表达为0.57±0.12,Notch3mRNA表达为0.62±0.12,Jagged1mRNA表达为0.43±0.06,HeslmRNA表达为0.60±0.14;益气养阴高剂量组Notch1mRNA表达为0.07±0.05,Notch3mRNA表达为0.05±0.02,Jagged1mRNA表达为0.18±0.07,HeslmRNA表达为0.17±0.04;药物干预组Notch1mRNA表达均较模型组低(P<0.05),等效剂量组Notch1mRNA表达高于CTX组(P<0.05);高剂量组较等效剂量组及CTX组Notch1mRNA表达量低(P<0.05);等效剂量组、高剂量组、CTX组Notch3mRNA表达均较模型组降低(P<0.05),等效剂量组Notch3mRNA表达与CTX组比较无统计学差异(P>0.05);高剂量组较等效剂量组及CTX组Notch3mRNA表达量降低(P<0.05);等效剂量组、高剂量组、CTX组Jagged1mRNA及HeslmRNA表达均较模型组降低(P<0.05),等效剂量组与CTX组Jagged1mRNA及HeslmRNA表达量降低,(P>0.05);高剂量组较等效剂量组及CTX组Jagged1mRNA及HeslmRNA表达量降低(P<0.05)。结论:益气养阴方剂有抑制Lewis肺癌移植小鼠肿瘤生长的作用,且较大剂量的益气养阴方用量更有利于抑制Lewis肺癌细胞生长,而这种抑制作用与益气养阴方剂调控肿瘤组织中Notch1信号通路有关。

Objective： To invesgate the relationship between the effect of Yiqi Yangyin Decoction on supressing tumor-bearing Lewis lung cancer mice and discuss the medchanism through the Notch signal pathway. Methods： Sixty inbred C57BL/6 mice bearing Lewis lung cancer were randomly indived into four groups： model group（ A group）,CTX chemotherapy group（ B group）,Yiqi Yangyin equivalent dose group（ C group）,Yiqi Yangyin high dose group（ D group）,each group had 15 mice. The mice in A group were only made modesl. The mice in B group were induced by intraperitoneal injection of CTX according 20 mg/kg every week. The mice in C group were treated with Yiqi Yangyin Decoction of 0. 345mL/g by gastric lavage. The mice in D group were treated with Yiqi Yangyin Decoction of 1. 36 mL/g by gastric lavage.All mice were treated for 30 days and fed with commercial diet. At the same time,the tumor volume was recorded. And then all the rats were sacrificed and all tumor tissues were made HE sections routinely,meanwhile the Notch signal expression in tumor tissues was tested. Results：（1）Relative tumor volume（ RTV） and relative suppressing-tumor rate： RTV of each group except model group was reduced. RTV of B,C and D group were reduced more than that of A group（ P〈0. 01）. RTV of D group was reduced mostly among four groups. RTV of B group was reduced more than that of C group（ P〈0. 05）. The relative suppressing-tumor rate of D group was the highest among the four groups（ P〈0. 05）. The rate of B group was higher than that of C group（ P〈0. 05）.（2）The expression of Notch signal pathway： the expression of Notch1 mRNA in B,C and D group were lower than that in A group（ P〈0. 05）. The expression of Notch1 mRNA in C group was higher than that in B group（ P〈0. 05）,but the expression of Notch1 mRNA in D group was the lowest among B,C and D group（ P〈0. 05）. The change of the expression of Jagged1 mRNA,HeslmRNA and Notch3 mRNA were familiar with the change of Notch1 mRNA in four groups（ P〈0. 05）,but the expression of Notch3 mRNA between C group and B group was not signficant（ P〉0. 05）. Conclusion： Yiqi Yangyin Decoction can suppress the Lewis lung cancer cell. More Yiqi Yangyin Decoction can better suppress the cancer cell. The medchanism may be that Yiqi Yangyin Decoction can mediate the expression of Notch1 signal pathway.