摘要
目的探讨白花蛇舌草(HDW)对移植瘤肺癌小鼠肿瘤的抑制作用及对磷脂酰肌醇激酶(PI3K)/蛋白激酶B(Akt)信号通路和趋化因子受体9(CCR9)、趋化因子25(CCL25)表达的影响。方法体外培养Lewis肺癌细胞株,将对数期细胞接种于C57BL/6J雄性小鼠腋下皮肤建立移植瘤模型。将造模成功的30只小鼠随机分为模型组、低剂量HDW组和高剂量HDW组,每组10只。低、高剂量HDW组小鼠分别给予HDW乙醇提取物5、20 g·kg-1,灌胃,每日1次,连续4周;模型组小鼠给予等体积的生理盐水。末次给药后称小鼠体质量,然后颈椎脱臼处死小鼠,取出瘤体测质量,并计算肿瘤体积、抑瘤率及肺脏指数。免疫组织化学法检测小鼠肺癌组织中CCR9、CCL25的表达;Western blot法检测小鼠肺癌组织中PI3K、Akt、磷酸化Akt(p-Akt)蛋白的表达。结果低剂量HDW组和模型组小鼠肺脏指数比较差异无统计学意义(P>0.05);高剂量HDW组小鼠肺脏指数显著低于模型组和低剂量HDW组(P<0.05)。高、低剂量HDW组小鼠肺癌体积和瘤体质量均显著小于模型组,抑瘤率高于模型组(P<0.05);高剂量HDW组小鼠肺癌体积和瘤体质量显著小于低剂量HDW组,抑瘤率高于低剂量HDW组(P<0.05)。高、低剂量HDW组小鼠肺癌组织中CCR9、CCL25表达量均显著低于模型组(P<0.05)。高剂量HDW组小鼠肺癌组织中CCR9、CCL25表达量显著低于低剂量HDW组(P<0.05)。高、低剂量HDW组小鼠肺癌组织中p-Akt、PI3K蛋白的表达量均显著低于模型组(P<0.05);高剂量HDW组小鼠肺癌组织中p-Akt、PI3K蛋白的表达量显著低于低剂量HDW组(P<0.05);3组小鼠肿瘤组织中Akt蛋白表达比较差异无统计学意义(P>0.05)。结论HDW可显著抑制Lewis肺癌移植瘤小鼠肿瘤的生长,降低小鼠的肺脏指数,该作用可能与其抑制CCR9/CCL25表达进而调节PI3K/Akt信号通路蛋白有关。
Objective To investigate the inhibitory effect of Hedyotis diffusa willd(HDW)on tumor in transplanted lung cancer mice and its effect on the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)signaling pathway proteins and the expression of C-C chemokine receptor 9(CCR9)and C-C chemokine ligand 25(CCL25).Methods Lewis lung cancer cell lines were cultured in vitro,and the log phase cells were inoculated into the subcutaneous skin of male C57BL/6J mice to establish transplanted tumor model.Thirty model mice were randomly divided into model group,low dose HDW group and high dose HDW group after the successful establishment of the model,with 10 rats in each group.The mice in the low dose HDW group and high dose HDW group were given HDW ethanol extract 5,20 g·kg-1 respectively,once a day for 4 weeks;the mice in the model group were given the same volume of normal saline.After weighing the body weight,the mice were sacrificed by cervical dislocation and the tumor was taken to measure the weight and volume.The tumor inhibition rate and lung index were calculated.The expression of CCR9 and CCL25 in lung cancer tissues were detected by immunohistochemistry.The expressions of PI3K,Akt and phosphorylation protein kinase B(p-Akt)protein in lung cancer tissues were detected by Western blot.Results There was no significant difference in the lung index between the low dose HDW group and model group(P>0.05);the lung index of mice in the high dose HDW group was significantly lower than that in the model group and low dose HDW group(P<0.05).Compared with the model group,the tumor volume and tumor mass of mice in the high dose HDW group and low dose HDW group were significantly reduced,and the tumor inhibition rate was significantly increased(P<0.05).Compared with the low dose HDW group,the tumor volume and tumor mass of mice in the high dose HDW group were significantly reduced,and the rumor inhibition rate was significantly increased(P<0.05).The relative expression of CCR9,CCL25 and the expressions of p-Akt and PI3K protein in lung cancer tissues of mice in the high dose HDW group and low dose HDW group were significantly lower than those in the model group(P<0.05);the expressions of CCR9,CCL25and p-Akt,PI3K protein in lung cancer tissues of mice in the high dose HDW group were significantly lower than those in the low dose HDW group(P<0.05);there was no significant difference in the expression of Akt protein in lung cancer tissues of mice among the three groups(P>0.05).Conclusion HDW can significantly inhibit the growth of transplanted tumor in Lewis lung cancer mice and decrease the lung index of mice,which may be related to inhibiting CCR9,CCL25 expression and regulating PI3K/Akt signaling pathway proteins.
作者
陈鑫
李劲鸿
田晓峰
CHEN Xin;LI Jinhong;TIAN Xiaofeng(Department of Pharmacy,Tieling Central Hospital,Tieling 112000,Liaoning Province,China)
出处
《新乡医学院学报》
CAS
2020年第3期230-234,共5页
Journal of Xinxiang Medical University
基金
2017年辽宁省自然科学基金指导计划立项项目(编号:20170540559)。
关键词
白花蛇舌草
肺癌
移植瘤
趋化因子受体9
趋化因子25
磷脂酰肌醇激酶/蛋白激酶B信号通路
Hedyotis diffusa willd
lung cancer
transplanted tumor
C-C chemokine receptor 9
C-C chemokine ligand 25
phosphatidylinositol 3 kinase/phosphorylation protein kinase B signaling pathway
作者简介
陈鑫(1984-),男,辽宁铁岭人,学士,主管药师,研究方向:临床药学。
