PinX1基因对结直肠癌预后及5-FU化疗敏感性的影响  

Effects of PinX1 gene on the prognosis and 5-FU sensitivity of colorectal cancer

作　　者：李泳澄 王翔[2] 张有为[2] 袁媛[2] 韩正祥 LI Yongcheng;WANG Xiang;ZHANG Youwei;YUAN Yuan;HAN Zhengxiang(School of Clinical Medicine,Xuzhou Medical University,Xuzhou,Jiangsu 221004,China;Department ofMedical Oncology,Xuzhou Central Hospital,Xuzhou,Jiangsu 221009;Department of Medical Oncology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221002)

机构地区：[1]徐州医科大学临床学院,江苏徐州221004 [2]徐州市中心医院肿瘤内科,江苏徐州221009 [3]徐州医科大学附属医院肿瘤内科,江苏徐州221002

出　　处：《徐州医科大学学报》2020年第1期60-64,共5页Journal of Xuzhou Medical University

基　　金：徐州市科技局社会发展面上项目(KC17099)。

摘　　要：目的探讨PinX1(Pin2/TRF1 interacting protein X1)基因表达对结直肠癌(colorectal cancer,CRC)预后及5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。[JP2]方法GEPIA2在线工具分析PinX1在CRC组织的表达及预后。构建pEGFP-C3-PinX1过表达质粒,分别转染CRC细胞株LoVo和HT29细胞,CCK-8法检测细胞增殖、测定5-FU量效曲线并计算IC 50,实时定量PCR检测相对端粒长度(relative telomere length,RTL),流式细胞术检测细胞凋亡。结果PinX1高表达与CRC分期早及较好的总生存(overall survival,OS)有关。Western blot证实基因转染成功。PinX1过表达组LoVo和HT29细胞的增殖指数降低,5-FU的IC 50值降低,RTL降低,凋亡率增[JP2]加;联合小剂量5-FU(0.5 mg/L)干预后,RTL降低和凋亡增加更为显著。结论CRC患者PinX1基因高表达提示预后较好;PinX1过表达可抑制CRC细胞增殖,提高5-FU化疗敏感性,其机制可能与缩短端粒长度、诱导凋亡有关。ObjectiveTo explore the effects and mechanism of Pin2/TRF1 interacting protein X1(PinX1)gene on the prognosis and 5-fluorouracil(5-FU)sensitivity of colorectal cancer(CRC).MethodsThe expression and prognosis of PinX1 in CRC tissues were analyzed by online GEPIA2 database.A plasmid over-expression pEGFP-C3-PinX1 was constructed and transfected into CRC cell lines(LoVo and HT29).CCK-8 assay was used to determine cell proliferation.5-FU dose-response curve was plotted to calculate IC 50.Real-time quantitative PCR was performed to detect relative telomere length(RTL).Apoptosis was detected by flow cytometry.ResultsHigh expression of PinX1 was associated with early CRC staging and better overall survival(OS).According to Western blot,PinX1 was successfully transfected.In the PinX1 overexpression groups,LoVo and HT29 cells showed a declined proliferation rate,with decreases in the IC 50 value of 5-FU and RTL,and increases in apoptotic rate,compared to the empty vector group.The changes in RTL and apoptosis rate became more significantly after combined treatment with a low dose of 5-FU(0.5 mg/L).ConclusionsUp-regulation of PinX1 mRNA indicates better prognosis of CRC pateints.PinX1 overexpression can inhibit the proliferation of CRC cells and increase the sensitivity of 5-FU,which may be related to shortened telomere length and induced apoptosis.

关 键 词：PinXl 结直肠癌 5-氟尿嘧啶 化疗敏感性 

分 类 号：R735.35[医药卫生—肿瘤]