舌癌组织缺氧微环境中脂联素的表达与调控

Effects of hypoxia on adiponectin in tongue squamous cell carcinoma

目的:脂联素(adiponectin,APN)是一种内源性细胞因子,与多种肿瘤的发生发展密切相关。本研究旨在检测舌癌APN及其受体(AdipoR1和AdipoR2)的组织学表达分布特征,探讨APN在局部组织中的表达是否受到缺氧诱导因子HIF-1α的调控。方法:采用免疫组织化学检测舌癌组织中APN及其受体的表达分布特征;慢病毒包装HIF-1αshRNA载体并转染舌癌细胞构建稳定沉默HIF-1α的细胞系;应用RT-PCR和蛋白质印迹法(Western blot)检测APN及其受体mRNA和蛋白在缺氧条件下的表达变化。结果:在肿瘤发生早期,即当肿瘤体积较小(T1和T2期)或未发生淋巴结转移(N0期)时,肿瘤组织APN及AdipoR1的表达与癌旁正常上皮相比上调(P<0.05,<0.01),AdipoR2的表达无显著改变。将舌癌细胞缺氧后APN及AdipoR1的表达分别上调,但AdipoR2的表达不变。敲低HIF-1α表达后缺氧处理可同时下调APN及AdipoR1表达。结论:舌癌局部缺氧微环境下,APN-Adi poR1信号通路被激活,该过程受到HIF-1α的调控。

Objective:Adiponectin(APN)is an endogenous cytokine that mediates the development and progression of various tumors through its receptors(AdipoRs).The present study aimed to detect the expression and distribution of APN and its receptors(AdipoR1 and AdipoR2)in tongue squamous cell carcinoma(TSCC).Moreover,we explored whether the locoregional expression of APN was regulated by HIF-1αin the hypoxic microenvironment.Methods:The expression and distribution of APN and its receptors in TSCC tissues were analyzed by immunohistochemical.Lentiviral expression vector for HIF-1αshRNA was constructed and stably transfected in TSCC cells to knock down HIF-1αexpression.The mRNA and protein expression levels of APN and its receptors were detected using RT-PCR and Western blot,respectively,after hypoxic treatment.Results:The locoregional expression of APN and AdipoR1,but not AdipoR2,was upregulated at the early stages of T1,T2,and/or N0 stage,respectively,in tumor tissues compared to that in control paracancerous tissues(P<0.05 or P<0.01).The expression of APN and AdipoR1,but not AdipoR2,in TSCC cells was up-regulated on hypoxic treatment.Moreover,the expression of APN and AdipoR1 was down-regulated after shRNA knockdown of HIF-1αunder hypoxia.Conclusions:The APN-AdipoR1 signaling pathway was activated and regulated by HIF-1αin the hypoxic environment of TSCC tissues.