清燥救肺汤对Lewis肺癌小鼠EGFR,NF-κB,ICAM-1表达及JAK1,STAT1蛋白磷酸化的影响

Effect of Qingzao Jiufei Tang Expression on EGFR,NF-κB,ICAM-1 and Protein Phosphorylation of JAK1 and STAT1 of Lewis Lung Cancer in Rats

目的:观察清燥救肺汤对荷Lewis小鼠肺癌瘤重、瘤指数、检测核转录因子-κB(NF-κB),细胞间黏附分子-1(ICAM-1),两面神激酶1(JAK1),表皮生长因子(EGFR)表达及信号传导及转录激活因子1(STAT1)蛋白磷酸化的影响。方法:雄性C57BL/6J小鼠50只,随机分为模型组,化疗[50 mg·kg^(-1)·(2 d)-1]组,清燥救肺汤高、中、低剂量(15.2,7.6,3.8 g·kg^(-1)·d^(-1))组,每组10只。右腋下注射细胞建立荷Lewis肺癌小鼠模型,清燥救肺汤组以相应剂量造模前2周开始灌胃给药,环磷酰胺(CTX)组以CTX相应剂量腹腔注射给药,隔日1次,模型组以等体积生理盐水灌胃给药,2周后处死各组小鼠并取瘤组织,称定质量计算瘤指数,免疫组化法检测NF-κB蛋白表达,实时荧光定量PCR法检测ICAM-1 mRNA表达,蛋白免疫印迹法(Western blot)检测EGFR,p JAK1及p STAT1蛋白表达。结果:与模型组比较,清燥救肺汤高、中剂量组及CTX组瘤重、瘤指数显著降低(P<0.01),清燥救肺汤高、中剂量组及CTX组NF-κB蛋白表达,EGFR蛋白表达明显降低(P<0.05,P<0.01),清燥救肺汤高、中剂量组ICAM-1 mRNA,p JAK1蛋白表达明显降低(P<0.05,P<0.01),清燥救肺汤高、中、低剂量组p STAT1蛋白磷酸化显著降低(P<0.01),高、中剂量组效果优于CTX组(P<0.01)。结论:清燥救肺汤能显著抑制荷Lewis小鼠肺癌细胞增殖,其机制可能与降低NF-κB,ICAM-1,p JAK1,EGFR表达及抑制STAT1蛋白磷酸化有关。

Objective： To observe the effect of Qingzao Jiufei Tang（ QJT） on tumor weight,tumor index,nuclear transcription factor kappa B（ NF-κB）,intercellular cell adhesion molecule-1（ ICAM-1）,janus kinase 1（ JAK1）,epidermal growth factor receptor（ EGFR） and signal transducers and activators of transcription1（ STAT1） protein phosphorylation of Lewis lung cancer mice. Method： Totally 50 male C57 BL /6J mice were randomly divided into model group,chemotherapy group [50 mg·kg^（-1）·（ 2 d）- 1],and high,medium and low-dose QJT groups（ 15. 2,7. 6,3. 8 g·kg^（-1）·d^（-1））,with 10 in each group. The animal model was induced through the axillary injection with Lewis cells in the right arm of mice. QJT groups were intragastrically administered with medicines two weeks before modeling,chemotherapy group was intragastrically administered with cyclophosvnamide（ CTX） at the corresponding dose,once every other day,and model group was intragastrically administered with the same volume of saline. At 2 weeks after modeling,the mice were put to death to weigh the tumor index,detect the expression of NF-κB by immunohistochemical method,the expression of ICAM-1 by Real-time PCR method,and JAK1,p EGFR and p STAT1 by Western blot method. Result： Tumor weight and tumor index of high and mediumdose QJT groups and CTX group were significantly decreased,compared with the model group,with significant differences（ P〈0. 01）. CTX group,and high and medium-dose QJT groups showed significant decreases in the expression of NF-κB and EGFR protein expression（ P〈0. 05,P〈0. 01）,high and medium-dose QJT groups showed significant decrease in the expressions of ICAM-1 and p JAK1（ P〈0. 05,P〈0. 01）,high,medium and low-dose QJT groups showed significant decrease in phosphorylation of STAT1,compared with the model group,with significant differences（ P〈0. 01）,high and medium-dose QJT groups were superior to CTX group（ P〈0. 01）. Conclusion： QJT can significantly inhibit the proliferation of Lewis lung cancer cells. It may inhibit lung cancer by reducing the protein expressions of NF-κB,ICAM-1,p JAK1,EGFR,phosphorylation of STAT1 protein.