薄芝糖肽联合顺铂对食管鳞状细胞癌细胞增殖凋亡及相关信号通路的影响  

Effects of GCGP combined with cisplatin on proliferation,apoptosis,MAPK/ERK,and PI3K/Akt signaling pathways of esophageal squamous cell carcinoma

作　　者：薛晓婕[1,2,3] 李飞容 孙秋萍 XUE Xiaojie;LI Feirong;SUN Qiuping(Department of Clinical Laboratory,Huangshi Central Hospital of Edong Healthcare(The Affiliated Hospital of Hubei Polytechnic University),Huangshi 435000,China;不详)

机构地区：[1]鄂东医疗集团黄石市中心医院(湖北理工学院附属医院)检验科,湖北黄石435000 [2]肾脏疾病发生与干预湖北省重点实验室 [3]武汉科技大学医学院 [4]鄂东医疗集团黄石市中心医院(湖北理工学院附属医)

出　　处：《山东医药》2022年第2期22-25,共4页Shandong Medical Journal

基　　金：湖北省卫生健康委青年人才科研基金资助项目(WJ2019H449);湖北省医学青年拔尖人才。

摘　　要：目的观察薄芝糖肽(GCGP)注射液联合顺铂对食管鳞状细胞癌细胞的增殖凋亡的影响,并探讨其作用机制。方法取食管鳞状细胞癌Eca-109细胞株常规培养,分别加入50、100、200 mg/L GCGP溶液及100 ng/mL顺铂作用24、48、72 h,采用MTT法检测细胞增殖能力,因100 mg/L GCGP联合顺铂作用48 h时的IC50为44.1%,故选择该浓度和作用时间作为GCGP联合顺铂用药的最佳作用浓度和作用时间。另取Eca-109细胞,随机分为对照组、GCGP组、顺铂组、GCGP+顺铂组,对照组正常培养,GCGP组加入100 mg/L GCGP,顺铂组加入100 g/mL顺铂,GCGP+顺铂组加入100 mg/L GCGP和100 g/mL顺铂。采用细胞克隆技术观察各组细胞增殖能力,流式细胞术检测各组细胞凋亡情况,Western blotting法检测细胞中MAPK/ERK信号通路调控蛋白胰岛素样生长因子结合蛋白4(IGFBP-4)、妊娠相关血浆蛋白A(PAPP-A)、细胞外信号调节激酶(ERK)及PI3K/Akt信号通路调控蛋白尿激酶纤溶酶原激活物(uPA)、蛋白激酶B(Akt)蛋白的表达水平。结果与对照组比较,GCGP组、顺铂组和GCGP+顺铂组细胞集落形成率均降低,且GCGP+顺铂组细胞集落形成率低于GCGP组和顺铂组(P均<0.01)。与对照组比较,GCGP组、顺铂组、GCGP+顺铂组细胞凋亡率均升高,且GCGP+顺铂组细胞凋亡率显著高于GCGP组和顺铂组(P <0.05或<0.01)。与对照组比较,GCGP组、顺铂组和GCGP+顺铂组PAPP-A、uPA蛋白表达均下降,IGFBP-4、ERK、Akt蛋白表达均升高;与GCGP组和顺铂组比较,GCGP+顺铂组PAPP-A、uPA蛋白表达降低,IGFBP-4、ERK、Akt蛋白表达升高(P均<0.05)。结论 GCGP与顺铂联合用药相对于单独用药能够有效抑制ECA-109细胞增殖并诱导其凋亡,其作用机制可能与MAPK/ERK和PI3K/Akt信号通路激活有关。Objective To observe the effects of GCGP injection combined with cisplatin on proliferation and apoptosis of esophageal squamous cell carcinoma cells,and to investigate the mechanism.Methods EcA-109 cell line of esophageal squamous cell carcinoma was routinely cultured and treated with 50,100,and 200 mg/L GCGP solution and 100 ng/mL cisplatin for 24,48,and 72 h,respectively.Cell proliferation was detected by MTT.The results showed that the IC50 of 100 mg/L GCGP combined with cisplatin for 48 h was 44.1%,so this concentration and action time were selected as the optimal action concentration and action time of GCGP combined with cisplatin.Eca-109 cells were randomly divided into the control group,GCGP group,cisplatin group,and GCGP + cisplatin group.The cells in the control group were cultured normally,and the cells in the GCGP group were added with 100 mg/L GCGP,the cisplatin group with 100 g/mL cisplatin,and the GCGP + cisplatin group with 100 mg/L GCGP and 100 g/mL cisplatin,respectively.Cell proliferation was observed by cell cloning technology,apoptosis was detected by flow cytometry,and the relative expression levels of PAPP-A,IGFBP-4,uPA,ERK and Akt proteins were detected by Western blotting.Results Compared with the control group,the colony formation rates of the GCGP group,cisplatin group and GCGP + cisplatin group decreased,and the colony formation rate of the GCGP + cisplatin group was lower than those of the GCGP group and cisplatin group(all P < 0.01).Compared with the control group,the apoptosis rates of GCGP group,cisplatin group and GCGP + cisplatin group increased,and the apoptosis rate of the GCGP + cisplatin group was significantly higher than those of the GCGP group and cisplatin group(P< 0.05 or P < 0.01).Compared with the control group,the protein expression levels of PAPP-A and uPA in the GCGP group,cisplatin group and GCGP + cisplatin group decreased,while the protein expression levels of IGFBP-4,ERK and Akt increased.Compared with the GCGP group and the cisplatin group,the expression levels

关 键 词：食管鳞状细胞癌 薄芝糖肽 顺铂 PAPP IGFBP-4 UPA ERK Akt 

分 类 号：R735.1[医药卫生—肿瘤]