文献类型：期刊文献

中文题名：基于PI3K/Akt/mTOR信号通路探讨归芪益元膏联合顺铂治疗Lewis肺癌的作用

英文题名：Role of Guiqi Yiyuan ointment combined with cisplatin in the treatment of Lewis lung cancer based on PI3K/Akt/mTOR signal pathway

作者：袁超[1];孔思琪[1];梁建庆[2];张毅[1];胡蓉[1];张悦[1];刘瑜[1];李金田[1]

第一作者：袁超

机构：[1]甘肃中医药大学中医临床学院,甘肃兰州730000;[2]甘肃中医药大学基础医学院,甘肃兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2024

卷号：40

期号：10

起止页码：1424

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金资助项目(82160872);甘肃省教育厅“双一流”科研重点基金资助项目(GSSYLXM-05);甘肃省中医药研究中心开放课题基金资助项目(zyzx-2020-zx17);中医学一级学科“岐黄英才”导师专项基金资助项目(2022-13)。

语种：中文

中文关键词：归芪益元膏;顺铂;肺癌;磷脂酰化醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路;凋亡;自噬;增效减毒

外文关键词：Guiqi Yiyuan ointment;cisplatin;lung cancer;phosphoinositide 3-kinase/protein kinase B/mammalian rapamycin target protein signal pathway;apoptosis;autophagy;synergism and detoxification

摘要：目的观察归芪益元膏对Lewis肺癌小鼠肿瘤生长的抑制作用,探讨归芪益元膏联合顺铂通过磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路抗肿瘤的分子机制。方法将60只C57BL/6小鼠随机分为6组,每组10只,除空白组(0.9%NaCl)外,其余均建立Lewis肺癌荷瘤小鼠模型,将荷瘤小鼠随机分为模型组(0.9%NaCl)、对照组(0.9%NaCl,顺铂5 mg·kg^(-1))和低、中、高剂量实验组(归芪益元膏1.6、3.3、6.6 g·kg^(-1),顺铂5 mg·kg^(-1))。以流式细胞术检测小鼠骨髓髓源性抑制细胞(MDSCs)水平;以蛋白质印迹法检测肿瘤组织中相关蛋白的表达。结果对照组和低、中、高剂量实验组的抑瘤率分别为(39.87±4.45)%、(45.74±14.97)%、(57.78±4.70)%和(69.82±11.05)%。空白组、模型组、对照组及低、中、高剂量实验组的骨髓中MDSCs占比分别为(36.13±1.08)%、(68.63±2.94)%、(58.93±2.02)%、(58.00±1.50)%、(50.93±5.06)%和(43.07±2.41)%。模型组、对照组和低、中、高剂量实验组p-PI3K/PI3K蛋白表达分别为0.97±0.03、0.77±0.02、0.72±0.01、0.68±0.03和0.53±0.02,PTEN分别为0.21±0.07、0.65±0.07、0.74±0.06、0.99±0.13和1.11±0.13,p-Akt/Akt分别为1.01±0.02和0.82±0.02、0.77±0.00、0.72±0.03和0.52±0.04,p-mTOR/mTOR分别为1.01±0.01、0.76±0.05、0.69±0.07、0.59±0.06和0.47±0.06;低、中、高剂量实验组与对照组比较,在统计学上差异均有统计学意义(均P<0.05)。结论归芪益元膏联合顺铂能明显改善小鼠生存质量及抑制肿瘤生长,其机制可能是抑制PI3K/Akt/mTOR信号通路,增强肿瘤细胞凋亡及自噬。
Objective To observe the inhibitory effect of Guiqi Yiyuan ointment on tumor growth in mice with Lewis lung cancer,and to explore the molecular mechanism of Guiqi Yiyuan ointment combined with cisplatin through phosphoinositide 3-kinase/protein kinase B/mammalian rapamycintarget protein(PI3K/Akt/mTOR)signal pathway.MethodssSixty C57BL/6 mice were randomly divided into 6 groups with 10 mice in each group.Except for the blank group(0.9%NaCl),Lewis lung cancer-bearing mice were randomly divided into model group(0.9%NaCl),control group(0.9%NaCl,cisplatin 5 mg·kg^(-1))and low,medium,high dose experimental groups(Guiqi Yiyuan ointment 1.6,3.3,6.6 g·kg^(-1),cisplatin 5 mg·kg^(-1)).Flow cytometry was used to detect bone marrow-derived suppressor cells(MDSCs);the expression of related proteins in tumor tissues was detected by Western blot.Results The tumor inhibition rates in control group and low,medium,high dose experimental groupswere(39.87±4.45)%,(45.74±14.97)%,(57.78±4.70)%and(69.82±11.05)%.The proportion of MDSCs in bone marrow of in blank group,model group,control group and low,medium,high dose experimental groups were(36.13±1.08)%,(68.63±2.94)%,(58.93±2.02)%,(58.00±1.50)%,(50.93±5.06)%and(43.07±2.41)%.The protein expressions of p-PI3K/PI3K in model group,control group and low,medium and high experimental groups were 0.97±0.03,0.77±0.02,0.72±0.01,0.68±0.03 and 0.53±0.02;PTEN were 0.21±0.07,0.65±0.07,0.74±0.06,0.99±0.13,1.11±0.13;p-Akt/Akt were 1.01±0.02,0.82±0.02,0.77±0.00,0.72±0.03 and 0.52±0.04;p-mTOR/mTOR were 1.01±0.01,0.76±0.05,0.69±0.07,0.59±0.06 and 0.47±0.06.There were significant differences between low,medium,high experimental groups and control group(all P<0.05).Conclusion Guiqi Yiyuan ointment combined with cisplatin can significantly improve the quality of life and inhibit tumor growth in mice.The mechanism may be the inhibition of PI3K/Akt/mTOR signal pathway and the enhancement of tumor cell apoptosis and autophagy.