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目的:通过研究ST3β-半乳糖苷α-2,3唾液酸转移酶5(ST3β-galactosideα-2,3-sialyltransferase 5,ST3GAL5)在人急性粒细胞白血病(acute myeloid leukemia,AML)NB4及其耐药细胞株NB4/ADR的差异表达,明确ST3GAL5对白血病细胞体内及体外药敏性的影响。方法:采用Real-time PCR和Western blotting技术检测人AML细胞株ST3GAL5的表达情况。特异性调控ST3GAL5,MTT及小鼠移植瘤模型实验检测干扰前后NB4和NB4/ADR细胞在体内、外对化疗药物敏感性的变化、PI3K/Akt信号通路的激活情况。结果:ST3GAL5在亲本细胞株NB4中高表达,在耐药细胞株NB4/ADR中低表达;特异性上调NB4/ADR细胞中ST3GAL5的表达,该细胞的药物敏感性增强(P<0.05),PI3K/Akt信号通路分子和P-gp表达降低(P<0.05);特异性下调NB4细胞中ST3GAL5的表达,该细胞的药物敏感性减弱,PI3K/Akt信号通路分子和P-gp表达升高。结论:ST3GAL5在人AML细胞及其耐药细胞株中表达均有显著差异,这些特征性改变与人AML多药耐药有关;AML多药耐药性可能是通过ST3GAL5介导PI3K/Akt信号通路分子和P-gp表达的改变实现。
Objective: To investigate the effect of ST3β-galactoside α-2,3-sialyltransferase 5 (ST3GAL5) on the proliferation and differentiation of human acute myeloid leukemia (AML) Differentially expressed NB4 / ADR cell lines, clear ST3GAL5 leukemia cell in vitro and in vivo susceptibility. Methods: Real-time PCR and Western blotting were used to detect the expression of ST3GAL5 in human AML cell line. Specific regulation of ST3GAL5, MTT and mouse xenograft model experiments before and after interference with NB4 and NB4 / ADR cells in vitro and in vivo chemosensitivity changes, PI3K / Akt signaling pathway activation. Results: ST3GAL5 was overexpressed in parental cell line NB4 and down-regulated in NB4 / ADR resistant cell line. The ST3GAL5 expression was up-regulated in NB4 / ADR cells (P <0.05) Akt signaling pathway and P-gp expression were down-regulated (P <0.05). The expression of ST3GAL5 was down-regulated in NB4 cells. The drug sensitivity of the cells was weakened, and the expression of PI3K / Akt signaling molecules and P-gp increased. Conclusion: The expression of ST3GAL5 in human AML cells and its drug-resistant cell lines are significantly different, and these characteristic changes are associated with human AML multidrug resistance; multidrug resistance of AML may be mediated through ST3GAL5 PI3K / Akt signaling pathway Molecular and P-gp expression is achieved.