SOX2在胰腺癌干细胞干性和化疗耐药中的作用及机制研究  

The Roles of SOX2 in Pluripotency Maintenance of Stem Cells and Chemotherapy Resistance in Pancreatic Cancer

作　　者：董云益 黄健 吕根生 DONG Yun-yi;HUANG Jian;LV Gen-sheng(The 904th Hospital of PLA,Suzhou 215000,China;Taikang Drum Tower Hospital,Nanjing 210046,China;Xinghai Hospital,Suzhou Industrial Park,Suzhou 215000,China)

机构地区：[1]解放军第904医院,江苏苏州215000 [2]泰康仙林鼓楼医院,江苏南京210046 [3]苏州工业园区星海医院,江苏苏州215000

出　　处：《肿瘤学杂志》2020年第4期318-322,共5页Journal of Chinese Oncology

摘　　要：[目的]探究性别决定相关基因簇2(SOX2)对胰腺癌干细胞干性与化疗耐药性的影响及影响机制。[方法]将培养至指数生长期胰腺癌干细胞随机分为SOX2抑制组、空白对照组与SOX2组,其中SOX2抑制组细胞与SOX2组细胞分别给予SOX2基因敲除与SOX2基因高表达处理,检测各组细胞SOX2 mRNA、八聚体结合转录因子4(OCT4)mRNA与谷胱甘肽过氧化物酶3(GPX3)mRNA表达水平;观察各组细胞增殖、侵袭及各组细胞对顺铂的耐药程度及在不同浓度顺铂处理下的凋亡情况。[结果] SOX2组细胞SOX2 mRNA与OCT4 mRNA表达水平明显高于SOX2抑制组与空白对照组细胞(P均=0.001);SOX2抑制组细胞增殖率与侵袭率明显低于空白对照组与SOX组(P<0.001);空白对照组细胞增殖率与侵袭率明显低于SOX2组(P<0.001);SOX2组细胞SOX2顺铂半数抑制浓度明显高于SOX2抑制组与空白对照组细胞(P<0.001);各浓度顺铂处理下的SOX2组细胞凋亡率均明显小于SOX2抑制组与空白对照组(P<0.001);SOX2组细胞GPX3 mRNA表达水平明显高于SOX2抑制组与空白对照组细胞(P<0.001)。[结论] SOX2能促进OCT4与GPX3表达,上调胰腺癌干细胞干性与化疗耐药性。[Objective] To investigate the roles of sex-determining region Y-box 2(SOX2) in pluripotency maintenance of stem cells and chemotherapy resistance in pancreatic cancer and the related mechanisms. [Methods] Pancreatic cancer stem cells(PCSCs) in the exponential growth phase were randomly divided into SOX2 inhibition group,blank control group and SOX2 group. PCSCs were transfected with SOXsh RNA in SOX2 inhibition group,and transfected with p-BRIT-SOX2 SOX2 plasmid in SOX2 overexpression group. The m RNA expression levels of SOX2,octamer binding transcription factor 4(OCT4)and glutathione peroxidase 3(GPX3) were detected. Cell proliferation,invasion,resistance to cisplatin and apoptosis rate under different concentrations of cisplatin were observed in each group. [Results]The m RNA expression levels of SOX2 and OCT4 in SOX2 group were significantly higher than those in SOX2 inhibition group and blank control group(all P=0.001). The cell proliferation and invasion rates of SOX2 inhibition group were significantly higher than those of SOX2 group and blank control group(P<0.001). The cell proliferation rate and invasion rate in the blank control group were significantly lower than those in the SOX2 group(P<0.001). The IC50 of cisplatin in SOX2 group was significantly higher than that in SOX2 group and blank control group(P<0.001). The apoptosis rate of SOX2 group treated with different concentrations of cisplatin was significantly lower than that of SOX2 inhibition group and blank control group(P<0.001). The m RNA expression of GPX3 in SOX2 group was significantly higher than that in SOX2 inhibition group and blank control group(P<0.001).[Conclusion] SOX2 can promote the expression of OCT4 and GPX3,up-regulate the stem cell and increase the chemotherapy resistance in pancreatic cancer.

关 键 词：SOX2 胰腺肿瘤 干细胞干性 化疗耐药性 作用机制 

分 类 号：R735.9[医药卫生—肿瘤]