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對順鉑耐藥的骨肉瘤細(xì)胞干細(xì)胞特性變化及其與Notch信號通路的關(guān)系

發(fā)布時間:2018-04-20 17:38

  本文選題:骨肉瘤 + 順鉑耐藥 ; 參考:《山東醫(yī)藥》2016年48期


【摘要】:目的探討對順鉑耐藥的骨肉瘤細(xì)胞干細(xì)胞特性變化及其與Notch信號通路的關(guān)系。方法取對數(shù)生長期的對順鉑耐藥的人骨肉瘤143B-TK細(xì)胞作為觀察組,以未經(jīng)順鉑作用的人骨肉瘤143B-TK細(xì)胞作為對照組。采用實(shí)時熒光定量PCR法檢測兩組干細(xì)胞相關(guān)基因(TERT、Sox2、Oct4、NANOG)、Notch信號通路相關(guān)基因(Hey L、Hey2、Hey1、Hes5、Hes1)mRNA相對表達(dá)量;兩組加入或不加入Notch信號通路特異性抑制劑DAPT,采用懸浮克隆球試驗檢測成球能力(以懸浮克隆球數(shù)量表示)。結(jié)果兩組NANOG、Hey2 mRNA相對表達(dá)量比較差異均無統(tǒng)計學(xué)意義(P均0.05)。觀察組TERT、Sox2、Oct4、Hey L、Hey1、Hes5、Hes1 mRNA相對表達(dá)量均高于對照組(P0.05或0.01)。不加入DAPT的觀察組懸浮克隆球數(shù)量明顯多于加入DAPT的觀察組和不加入DAPT的對照組(P均0.01)。結(jié)論對順鉑耐藥的骨肉瘤細(xì)胞干細(xì)胞特性增強(qiáng);Notch信號通路激活可能是導(dǎo)致其干細(xì)胞特性增強(qiáng)和細(xì)胞耐藥的主要原因。
[Abstract]:Objective to investigate the change of stem cell characteristics of cisplatin-resistant osteosarcoma cells and its relationship with Notch signaling pathway. Methods 143B-TK cells of cisplatin resistant human osteosarcoma at logarithmic growth stage were used as observation group and 143B-TK cells without cisplatin as control group. The relative expression of Hes5Hes1 mRNA in two groups of stem cell related genes, namely, Hes5Hes1 and Hes5Hes1, was detected by real-time fluorescence quantitative PCR assay. In two groups, Notch signaling pathway specific inhibitor DAPT was added or not, and the ability of spheroidization was tested by suspension clone ball test (expressed by the number of suspension clone balls). Results there was no significant difference in the relative expression of NANOGN Hey2 mRNA between the two groups (P < 0.05). The relative expression of hes5Hes1 mRNA in the observation group was higher than that in the control group (P0.05 or 0.01). The number of suspension clones in the observation group without DAPT was significantly higher than that in the observation group without DAPT and the control group without DAPT (P < 0.01). Conclusion the enhancement of stem cell characteristics of cisplatin resistant osteosarcoma cells and the activation of Notch signaling pathway may be the main reasons for the enhancement of stem cell characteristics and cell resistance of cisplatin resistant osteosarcoma cells.
【作者單位】: 武漢大學(xué)人民醫(yī)院;
【基金】:國家自然科學(xué)基金資助項目(81341078)
【分類號】:R738.1

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