盐酸安罗替尼联合多西他赛对肺癌大鼠血小板凝聚、EGFR-STAT3信号通路及抑瘤作用研究

Study of antirotinib hydrochloride combined with docetaxel on platelet aggregation,EGFR-STAT3 signaling pathway and antitumor effect in rats with lung cancer

目的探究盐酸安罗替尼联合多西他赛对肺癌大鼠血小板凝聚、EGFR-STAT3信号通路及抑瘤作用。方法选取清洁级雄性Wistar大鼠50只,分为健康组、模型组、盐酸安罗替尼组、多西他赛组、联合组,平均10只/组,除健康组外其余均建立肺癌模型,建模后健康组与模型组大鼠采用等量生理盐水灌胃干预,多西他赛组在大鼠静脉注射多西他赛0.3mg/kg。盐酸安罗替尼组采用盐酸安罗替尼1.2 mg·kg^(-1)·d^(-1)灌胃干预,联合组予以静脉注射0.3mg·kg^(-1)·d^(-1)多西他赛注射液同时盐酸安罗替尼1.2 mg·kg^(-1)·d^(-1)灌胃,干预30d。采用血小板聚集凝血因子分析仪对血小板凝聚率进行检测,HE染色观察肺部病理变化,对比肿瘤体积变化,免疫印迹及PCR分别检测表皮生长因子受体(EGFR)、信号转导与转录激活因子3(STAT3)蛋白及mRNA。结果与健康组比较,模型组大鼠的血小板聚集率、肿瘤体积、肺组织中EGFR、STAT3蛋白及mRNA均显著升高(P<0.05);与模型组比较,盐酸安罗替尼组和多西他赛组血小板聚集率、肿瘤体积、肺组织中EGFR、STAT3蛋白及mRNA均显著降低(P<0.05);与盐酸安罗替尼组和多西他赛组比较,联合组血小板聚集率、肿瘤体积、肺组织中EGFR、STAT3蛋白及mRNA均显著降低(P<0.05)。结论盐酸安罗替尼联合多西他赛在肺癌的治疗中对改善血小板凝聚、调节EGFR-STAT3信号通路以及抑制肿瘤生长等方面均具有一定积极效用。

Objective To investigate the effect of anrotinib hydrochloride combined with docetaxel on platelet aggregation,EGFR-STAT3 signaling pathway and tumor inhibition in rats with lung cancer.Methods 50 male clean grade Wistar rats were selected and divided into the healthy group,the model group,the arotinib hydrochloride group,the docetaxel group,and the combination group,with an average of 10 rats per group.Except for the healthy group,lung cancer models were established for all other rats.After modeling,the healthy group and model group rats were treated with equal amounts of physiological saline by gavage intervention,and the docetaxel group was injected with docetaxel 0.3mg/kg intravenously into the rats.The androtinib hydrochloride group received intravenous administration of 1.2 mg·kg^(-1)·d^(-1) of androtinib hydrochloride for intervention,while the combination group received intravenous injection of 0.3 mg·kg^(-1)·d^(-1) of docetaxel injection and intravenous administration of 1.2 mg·kg^(-1)·d^(-1) of androtinib hydrochloride for 30 days of intervention.Platelet aggregation factor analyzer was used to detect platelet aggregation rate,HE staining was used to observe pathological changes in the lungs,tumor volume changes were compared,and epidermal growth factor receptor(EGFR),signal transduction and transcription activating factor 3(STAT3)protein and mRNA were detected by immunoblotting and PCR,respectively.Results Compared with the healthy group,platelet aggregation rate,tumor volume,EGFR,STAT3 protein and mRNA in lung tissue of rats in the model group were significantly increased(P<0.05).Compared with the model group,the platelet aggregation rate,tumor volume,EGFR,STAT3 protein and mRNA in lung tissue of the androtinib hydrochloride and docetaxel groups were significantly decreased(P<0.05).Compared with the anrotinib hydrochloride group and the docetaxel group,platelet aggregation rate,tumor volume,EGFR,STAT3 protein and mRNA in lung tissue were significantly decreased in the combination group(P<0.05).Conclusion Antirotinib hydrochloride combined with docetaxel has certain positive effect on improving platelet aggregation,regulating EGFR-STAT3 signaling pathway and inhibiting tumor growth in treatment of lung cancer.