目的：通过研究ST3 β-半乳糖苷α-2,3唾液酸转移酶5（ST3 β-galactoside α-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 confirm the effect of ST3 β-galactosideα-2,3 sialyltransferase 5 (ST3GAL5) on drug resistance of AML in vivo and in vitro through studying the differential expression of ST3GAL5 between acute myeloid leukemia (AML) NB4 cell line and its drug-resistant cell line NB4/ADR. Methods: The expressions of ST3GAL5 in AML cell lines were detected by Real-time PCR and Western blotting assays. Expressions of ST3GAL5 in the cells were specifically regulated to increase or decrease. Before and after the interferences, Changes of sensitivities to chemotherapy drugs and activation of PI3K/Akt signaling pathway in the NB4 and NB4/ADR cells in vivo and in vitro were examined by MTT assay and experiments with xenograft mouse model. Results: ST3GAL5 was highly expressed in NB4 cell line but low expressed in its drug-resistant cell line NB4/ADR. Drug sensitivity and PI3K/Akt signaling pathway molecules of NB4/ADR cells in which expressions of ST3GAL5 were specifically up-regulated respectively increased and decreased (all P<0.05). Contrarily, drug sensitivity, PI3K/Akt signaling pathway molecules and P-gp of NB4 cells in which expressions of ST3GAL5 were down-regulated respectively decreased and increased. Conclusion: There were obvious differences of ST3GAL5 expressions between AML cell and its drug-resistant cell lines. These characteristic alterations are associated with multidrug resistance in AML, which is probably achieved through ST3GAL5 mediated-PI3K/Akt signaling pathway and alteration of P-gp expression.

国家自然科学基金资助项目（No. 81271910）