高表达CREB对食管腺癌细胞增殖、侵袭及NK细胞杀伤活性的影响  

Effects of upregulation of CREB on proliferation,invasion and NK cell killing activity of esophageal adenocarcinoma

作　　者：李程[1] 梁刚 霍斌亮[1] Li Cheng;Liang Gang;Huo Binliang(Department of Oncology,Shaanxi Provincial People's Hospital,Xi'an 710068,China;Department of General Surgery,Shaanci Nuclear Industry 215 Hospital,Xi'an 712000,China)

机构地区：[1]陕西省人民医院肿瘤外科,西安710068 [2]陕西省核工业二一五医院普通外科,西安712000

出　　处：《中国医师杂志》2021年第11期1637-1642,共6页Journal of Chinese Physician

基　　金：陕西省重点研发计划项目(2019SF-173)。

摘　　要：目的探讨cAMP反应元件结合蛋白(CREB)对食管腺癌细胞增殖、侵袭及NK细胞杀伤活性的影响。方法选取2017年3月至2019年12月陕西省人民医院收治的23例食管腺癌患者,免疫组织化学法检测食管腺癌组织和癌旁正常组织中CREB的蛋白表达,体外培养食管腺癌细胞TE-10,将转染si-NC的TE-10细胞设置为对照组,将转染si-CREB的TE-10细胞设置为si-CREB组。Western blot检测细胞中CREB、MHCⅠ类链相关蛋白A(MICA)与MHCⅠ类链相关蛋白B(MICB)的表达;流式细胞术检测MICA与MICB的表达;克隆形成实验与Transwell实验检测TE-10细胞的增殖及侵袭能力;乳酸脱氢酶释放法检测NK细胞对TE-10细胞的杀伤活性。结果食管腺癌组织中CREB的表达高于癌旁正常组织(P<0.05);食管腺癌细胞TE-10中CREB的蛋白表达量高于人正常食管上皮细胞HEEC(P<0.05)。si-CREB组TE-10细胞增殖及侵袭能力显著低于对照组(P<0.05),MICA与MICB的蛋白表达量、NK细胞对TE-10细胞的杀伤率显著高于对照组(P<0.05)。结论CREB在食管腺癌组织及细胞中高表达。沉默CREB可抑制食管腺癌细胞增殖与侵袭,上调MICA与MICB表达,增强NK细胞对食管腺癌细胞的杀伤敏感性。Objective To investigate the ffects of upregulation of cAMP response element binding protein(CREB)on proliferation,invasion and natural killer(NK)cell killing activity of esophageal adeno-carcinoma.Methods 23 patients with esophageal cancer treated in Shaanxi Provincial People's Hospital from March 2017 to December 2019 were selected.The protein expression of CREB in esophageal adenocar-cinoma and adjacent normal tissues was detected by immunohistochemistry;Esophageal adenocarcinoma cell line TE-10 was cultured in vitro.TE-10 cells transfected with si-NC were set as the control group and TE-10 cells transfected with si-CREB were set as the si-CREB group.Western blot was used to detect the protein level of CREB,MHC class Ⅰchain-related A(MICA)and MHC class Ⅰchain-related B(MICB);Flow cytometry was employed to detect the expression of MICA and MICB;clone formation experiment and Tran-swell were used to detect the proliferative and invasive ability of TE-10 cells;lactate dehydrogenase(LDH)releasing assay was used to dect cytotoxicity of NK cells against TE-10 cells.Results The expression of CREB in esophageal adenocarcinoma tissue was higher than that in normal tissues adjacent to cancer;the protein level of CREB in esophageal cancer cell TE-10 was higher than that of human normal esophageal epi-thelial cells HEEC(P<0.05).The proliferative and invasive ability of TE-10 cells in the si-CREB group was signifcant lower than that in the control group(P<0.05),while the expression of MICA and MICB,the killing rate of NK cells on TE-I0 cells was significant higher than that in the control group(P<O.05),Conclusions CREB was highly expressed in esophageal adenocarcinoma issues and cells.Silencing CREB could inhibit the proliferation and invasion of esophageal adenocarcinoma cells,and enhance the killing sensitivity of NK cells to csophageal adenocarcinoma cells by up-regulating the expression of MICA and MICB.

关 键 词：食管肿瘤 腺癌 CAMP反应元件结合蛋白质 杀伤细胞 天然 MHCⅠ类链相关蛋白A MHCⅠ类链相关蛋白B 

分 类 号：R735.1[医药卫生—肿瘤]