构建慢病毒介导缺氧诱导因子HIF-1α在宫颈癌细胞中的表达及其对裸鼠移植瘤的作用  

To construct lentivirus-mediated expression of hypoxia-inducing factor HIF-1αin cervical carcinoma and its effect on transplanted tumor in nude mice

作　　者：阿孜尔古丽·阿布都克日木[1,2,3] 马红 白冰[1] 阿瓦汗·吐尔迪 古丽仙·吐尔逊 于涛 AZIERGULI·Abudukerimu;MA Hong;BAI Bing;AWAHAN·Tuerdi;GLIXIAN·Tuerxun;YU Tao(School of Basic Medical Sciences,Xinjiang Medical University,Urumqi 830017,China;Key Laboratory of Molecular Biology of Endemic Diseases;State Key Experiment of Pathogenesis and Prevention of Highly Prevalent Diseases in Central Asia;Maternal and Child Healthcare Service Centre,Shaybak District;Tumour Hospital,Xinjiang Medical University;Shandong Institute of Parasitic Diseases,Shandong First Medical University)

机构地区：[1]新疆医科大学基础医学院,新疆乌鲁木齐830017 [2]新疆地方病分子生物学重点实验室 [3]中亚高发疾病发病机制与防治国家重点实验 [4]乌鲁木齐市沙依巴克区妇幼保健服务中心 [5]新疆医科大学附属肿瘤医院 [6]山东省寄生虫病防治研究所,山东第一医科大学(山东省医学科学院)

出　　处：《中国病原生物学杂志》2024年第7期756-760,767,共6页Journal of Pathogen Biology

基　　金：新疆维吾尔自治区自然科学基金项目(No.2022D01C185)。

摘　　要：目的 探讨使用慢病毒载体介导的HIF-1α对裸鼠宫颈癌移植瘤生长、增殖和转移的影响,并寻找宫颈癌新的基因治疗靶点。方法 采用慢病毒介导技术,分别在SiHa和C33a细胞中提高C33a细胞的HIF-1α表达,同时敲减SiHa细胞的HIF-1α表达。通过qRT-PCR和Western blot技术验证慢病毒转染后HIF-1α表达的效率,并构建裸鼠移植瘤模型。从而验证HIF-1α表达改变对裸鼠体内肿瘤形成、增殖速度、肿瘤体积和肿瘤重量的影响及HIF-1α表达改变对肿瘤发展过程的影响。结果 敲减和过表达HIF-1α的SiHa和C33a细胞分别注射于裸鼠左侧腋窝皮下,1周后形成肿瘤,4周后测量移植瘤体积。干扰HIF-1α的裸鼠移植瘤体积较对照组较小,两者差异具有统计学意义(P<0.05),即干扰HIF-1α对裸鼠瘤体的生长具有抑制作用;而HIF-1α过表达后,裸鼠移植瘤体积较对照组较大,两者差异具有统计学意义(P<0.05)。结论 HIF-1α的表达改变与宫颈癌细胞的增殖和恶化存在一定相关性,HIF-1α表达的改变可以调控肿瘤增殖过程。Objective To investigate the effect of HIF-1αmediated by lentivirus on the growth,proliferation and metastasis of transplanted cervical cancer in nude mice,and to find a new gene therapy target for cervical cancer.Methods The lavivirus-mediated hypoxia-inducing factor HIF-1αwas constructed to increase the expression of HIF-1αin cervical cancer cells SiHa and C33a cells,respectively,while knockdown the expression of HIF-1αin SiHa cells.Verification of the expression efficiency of HIF-1αafter transfection with lentivirus was achieved by means of qRT-PCR and Western blot in a transplanted tumor model from nude mice.Further confirmation of the effects of HIF-1αexpression changes on tumor formation,proliferation rate,volume,and weight were conducted through vivo experiments.The effect of HIF-1αexpression on tumor development was verified.Results SiHa and C33a cells with knockdown and overexpression of HIF-1αwere injected subcutaneously into the left axilla of nude mice.Tumor formation was observed 1 week later,and tumor volume was measured 4 weeks later.The findings revealed that interfering with HIF-1αin subcutaneous grafted nude mice resulted in a significantly lower tumor volume compared to the control group(P<0.05).This suggests that inhibiting HIF-1αeffectively suppresses tumor growth in nude mice.However,upon overexpression of HIF-1α,the subcutaneous tumor volume in nude mice was significantly higher than that of the control group(P<0.05).Conclusion The change of HIF-1αexpression is related to the proliferation and deterioration of cervical cancer cells,and the change of HIF-1αexpression can regulate the proliferation process of tumor.

关 键 词：宫颈癌 缺氧诱导因子-1α 裸鼠皮下移植瘤模型 稳定转染 

分 类 号：R737.33[医药卫生—肿瘤]