甲状旁腺素通过调控初级纤毛的表达促进软骨肉瘤细胞增殖和侵袭

发布时间：2018-10-30 15:25

【摘要】：目的探究甲状旁腺素(parathyroid hormone,PTH)对软骨肉瘤细胞增殖和侵袭能力的影响,及其与初始纤毛表达调控之间的相互关系。方法应用不同浓度PTH刺激软骨肉瘤细胞SW1353,缺氧诱导纤毛表达和水合氯醛破坏纤毛结构后,通过CCK8细胞活性实验,Western blot及Transwell实验检测SW1353细胞的增殖和侵袭能力,免疫荧光计数初始纤毛表达情况,荧光定量PCR检测相关目的基因GLI1、PTCH1和IFT88的表达情况。结果 PTH能促进软骨肉瘤细胞增殖,且呈浓度依赖性,其促增殖效应与纤毛结构的完整性有关;PTH能上调SW1353细胞的侵袭能力,增加基质金属蛋白酶MMP9的表达,破坏纤毛结构后,PTH促进软骨肉瘤的侵袭效应受到抑制;PTH下调SW1353细胞初始纤毛的数量,其效应与纤毛结构完整性有关;PTH能调控Hedgehog通路靶基因GLI1、PTCH1及纤毛功能相关基因IFT88的表达。结论 PTH能促进软骨肉瘤细胞的增殖和侵袭,同时抑制软骨肉瘤细胞初级纤毛的表达并影响其下游靶基因表达,PTH可能通过作用于初始纤毛来调控软骨肉瘤的恶性生物学特性。
[Abstract]:Objective to investigate the effect of parathyroid hormone (parathyroid hormone,PTH) on the proliferation and invasion of chondrosarcoma cells and its relationship with the regulation of initial cilia expression. Methods chondrosarcoma cells were stimulated with different concentrations of PTH to induce SW1353, anoxic cilium expression and chloral hydrate to destroy cilia structure. The proliferation and invasion of SW1353 cells were detected by CCK8 cell activity test, Western blot and Transwell assay. The initial ciliated expression was counted by immunofluorescence and the expression of GLI1,PTCH1 and IFT88 was detected by fluorescence quantitative PCR. Results PTH could promote the proliferation of chondrosarcoma cells in a concentration-dependent manner. PTH could up-regulate the invasion ability of SW1353 cells, increase the expression of matrix metalloproteinase MMP9, and inhibit the invasion of chondrosarcoma promoted by PTH after the destruction of ciliated structure. PTH down-regulated the number of initial cilia in SW1353 cells and its effect was related to the structural integrity of cilia, and PTH could regulate the expression of GLI1,PTCH1 gene and IFT88 gene associated with cilium function in Hedgehog pathway. Conclusion PTH can promote the proliferation and invasion of chondrosarcoma cells and inhibit the expression of primary cilia and affect the downstream target gene expression of chondrosarcoma cells. PTH may regulate the malignant biological characteristics of chondrosarcoma by acting on the initial cilia.
【作者单位】：华中科技大学同济医学院附属同济医院骨科;华中科技大学同济医学院附属武汉中西医结合医院肿瘤科;
【基金】：国家自然科学基金资助项目(No.81672652) 湖北省自然科学基金青年基金资助项目(No.2015CFB213)
【分类号】：R738.1

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