高压氧联合替莫唑胺通过PI3K通路调节胶质瘤U87细胞的恶性生物学行为

来源 :中华航海医学与高气压医学杂志 | 被引量 : 0次 | 上传用户:jiansilang2006
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目的:探讨高压氧(HBO)联合替莫唑胺通过PI3K通路调节胶质瘤U87细胞的恶性生物学行为及其作用机制。方法:U87细胞培养完成后,按照数字表法随机分为对照组、替莫唑胺组、替莫唑胺+HBO组和HBO组,分别通过MTT法和流式细胞术检测细胞增殖能力和凋亡率。通过裸鼠皮下成瘤实验分析替莫唑胺联合HBO对U87细胞成瘤能力的影响。通过qPCR和Western blotting实验检测胶质瘤组织中缺氧诱导因子-1α(HIF-1α)mRNA和PI3K/AKT通路蛋白的表达水平。结果:与对照组比较,替莫唑胺组和HBO组U87细胞的增殖能力降低,凋亡率增高,HIF-1α和PI3K/AKT通路蛋白表达水平显著降低(n P<0.05)。替莫唑胺+HBO组U87细胞的增殖能力显著低于替莫唑胺组和HBO组,凋亡率显著高于替莫唑胺组和HBO组,HIF-1α和PI3K/AKT通路蛋白表达水平显著低于替莫唑胺组和HBO组(n P<0.05)。替莫唑胺可显著抑制胶质瘤的生长,并下降HIF-1α、PI3K和AKT磷酸化水平(n P<0.05);联合HBO可进一步抑制胶质瘤的生长,抑制HIF-1α和PI3K/AKT通路蛋白表达(n P<0.05)。n 结论:在替莫唑胺化疗的基础上联合HBO可能通过抑制PI3K通路和HIF-1α的表达,抑制胶质瘤U87细胞的增殖,并促进细胞凋亡,从而起到化疗增敏作用。“,”Objective:To explore the effect and action mechanism of temozolomide combined with hyperbaric oxygen (HBO) on regulating the malignant biological behavior of glioma U87 cells via PI3K pathway.Methods:After being cultured, the U87 cells were divided into control group, temozolomide group, temozolomide + HBO group, and HBO group, according to the random number table. The cell proliferation capacity and apoptosis rate were detected by MTT assay and flow cytometry respectively. The effect of temozolomide combined with HBO on tumorigenicity of the U87 cells was analyzed in vivo by subcutaneous tumorigenesis experiments in nude mice. The levels of hypoxia inducible factor (HIF) -1α mRNA and PI3K/AKT pathway-related protens were detected by Quantitative Polymerase Chain Reaction (qPCR) and Western blotting.Results:Compared with the control group, in the temozolomide group and the HBO group, the proliferation abilities of the U87 cells decreased, their apoptosis rate increased, and the levels of HIF-1α and PI3K/AKT pathway-related protens decreased significantly (n P<0.05). The proliferation ability of the U87 cells in the temozolomide + HBO group was weaker than those in the temozolomide group and the HBO group, while its apoptosis rate was significantly higher than the rates in the two group (n P<0.05). The levels of HIF-1α and PI3K/AKT pathway-related protens of the temozolomide + HBO group were significantly lower than those of the temozolomide group and the HBO group (n P<0.05). Temozolomide could significantly inhibit glioma growth, the HIF-1α level, and the phosphorylation levels of PI3K/AKT pathway (n P<0.05). When combined with HBO, temozolomide could further inhibit glioma growth, HIF-1α expression, and PI3K/AKT pathway (n P<0.05).n Conclusion:Temozolomide chemotherapy combined with HBO can suppress the proliferation of glioma U87 cells and promote apoptosis, therefore, improve the sensitivity of tumor cells; and these might be achieved by inhibiting PI3K pathway and the expression of HIF-1α.
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