丙泊酚调控PI3K/AKT信号通路对肺癌细胞增殖、迁移和凋亡的影响  

Effects of Propofol Regulating PI3K/AKT Signaling Pathway on Proliferation, Migration and Apoptosis of Lung Cancer Cells

作　　者：谢圆媛[1] 胡海峰[2] 赵莉[3] 薛鹏[4] XIE Yuan-yuan;HU Hai-feng;ZHAO Li;XUE Peng(Department of Geriatrics,the Affiliated Hospital of Yan'an University,Yan'an,Shaanxi 716000,China;Department of Oncology,the Affiliated Hospital of Yan'an University,Yan'an,Shaanxi 716000,China;Department of Vasculocardiology,the Affiliated Hospital of Yan'an University,Yan'an,Shaanxi 716000,China;Department of Anesthesiology,the Affiliated Hospital of Yan'an University,Yan'an,Shaanxi 716000,China)

机构地区：[1]延安大学附属医院老年病科,陕西延安716000 [2]延安大学附属医院肿瘤科,陕西延安716000 [3]延安大学附属医院心血管内科,陕西延安716000 [4]延安大学附属医院麻醉科,陕西延安716000

出　　处：《临床误诊误治》2021年第6期107-112,共6页Clinical Misdiagnosis & Mistherapy

基　　金：陕西省科技计划项目(2019ZP07258)。

摘　　要：目的探讨丙泊酚调控PI3K/AKT信号通路对肺癌细胞增殖、迁移和凋亡的影响。方法传代培养人肺癌A549细胞株,根据细胞培养基中添加丙泊酚浓度的不同分为control组(未添加丙泊酚)、pL组(添加丙泊酚1.5μg/ml)和pH组(添加丙泊酚2.2μg/ml);克隆形成实验、细胞划痕实验及流式细胞术检测丙泊酚对肺癌细胞增殖能力、迁移能力及细胞凋亡的影响,qRT-PCR和Western blot检测丙泊酚对PI3K/AKT信号通路相关蛋白(PTEN、PI3K、AKT和mTOR)表达的影响。采用苯并芘诱导雄性A/J小鼠肺癌模型,造模成功的小鼠被随机分为c组(腹腔注射0.9%氯化钠注射液)、p1组(腹腔注射丙泊酚20 mg/kg)和p2组(腹腔注射丙泊酚50 mg/kg),每组8只;观察丙泊酚对A/J小鼠体内肺癌的影响。结果与control组比较,pL组和pH组均能抑制A549细胞增殖和迁移能力,促进A549细胞的凋亡(P<0.05,P<0.01),且呈剂量依赖性。与control组比较,pL组和pH组均能抑制A549细胞中PI3K、AKT及mTOR mRNA和蛋白的表达,提高PTEN mRNA和蛋白的表达(P<0.01),且呈剂量依赖性。与c组比较,p1组和p2组肿瘤数量显著减少、肿瘤体积显著减小(P<0.05,P<0.01)。结论丙泊酚通过抑制PI3K/AKT信号通路的激活,从而抑制肺癌细胞的增殖、迁移能力,并促进其凋亡。Objective To explore effects of Propofol regulating PI3K/AKT signaling pathway on proliferation,migration and apoptosis of lung cancer cells.Methods The human lung cancer A549 cell line was subcultured and divided into control group(without Propofol),pL group(with 1.5μg/ml Propofol)and pH group(with 2.2μg/ml Propofol)according to different concentration of Propofol in cell culture medium.Clone formation experiment,cell scratch experiment and flow cytometry were employed to detect effects of Propofol on proliferation,migration and apoptosis of lung cancer cells,and quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot methods were used to detect effects of Propofol on expressions of PI3K/AKT signaling pathway related proteins(PTEN,PI3K,AKT and mTOR).Benzopyrene was used to induce lung cancer models in male A/J mice.The successfully mouse models were randomly divided into group c(n=8,intraperitoneal injection of 0.9%Sodium Chloride injection)and group p1(n=8,intraperitoneal injection of 20 mg/kg Propofol)and group p2(n=8,intraperitoneal injection of 50 mg/kg Propofol).The effect of Propofol on A/J mice with lung cancer was observed.Results Compared with those in control group,both pL and pH groups could inhibit proliferation and migration of A549 cells,and promote apoptosis of A549 cells(P<0.05,P<0.01),which showed a dose-dependent manner.Compared with those in control group,both pL and pH groups could inhibit expressions of PI3K,AKT and mTOR mRNA and proteins in A549 cells,and increase expressions of PTEN mRNA and proteins(P<0.01),which showed a dose-dependent manner.Compared with those in group c,numbers of tumors in group p1 and p2 were significantly reduced,and tumor volumes were significantly reduced(P<0.05,P<0.01).Conclusion Propofol inhibits proliferation and migration ability and promote apoptosis of lung cancer cells by inhibiting activation of the PI3K/AKT signaling pathway.

关 键 词：肺肿瘤 丙泊酚 PI3K/AKT信号通路 细胞增殖 细胞迁移 细胞凋亡 小鼠 

分 类 号：R734.2[医药卫生—肿瘤] R-332[医药卫生—临床医学]