Zhang Xu, Dong Weijie, Zhou Huimin, Li Hongshuai, Wang Ning, Miao Xiaoyan, Jia Li
Department of Medical Laboratory, College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China.
IUBMB Life. 2015 Feb;67(2):77-87. doi: 10.1002/iub.1351. Epub 2015 Apr 9.
Cell surface sialylation is emerging as an important feature of cancer cell multidrug resistance (MDR). We have focused on the influence of 2,8-sialyltransferases in key steps of the development of MDR in chronic myeloid leukemia (CML). The expressional profiles of six α-2,8-sialyltransferases were generated in three pairs of CML cell lines and peripheral blood mononuclear cells (PBMC) of CML patients. Cellular MDR phenotype positively correlated with ST8SIA4 and ST8SIA6 levels. Furthermore, ST8SIA4 mediated the activity of phosphoinositide-3 kinase (PI3K)/Akt signal pathway and the expression of P-glycoprotein (P-gp). Targeting the PI3K/Akt pathway by its specific inhibitor LY294002, or by Akt RNA interfering reversed the MDR phenotype of K562/ADR cells. Inhibition of PI3K/Akt pathway also attenuated the effects caused by the overexpression of ST8SIA4 on MDR. Therefore this study indicated that α-2,8-sialyltransferases involved in the development of MDR of CML cells probably through ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp.
细胞表面唾液酸化正成为癌细胞多药耐药性（MDR）的一个重要特征。我们聚焦于2,8-唾液酸转移酶在慢性髓性白血病（CML）多药耐药性发展关键步骤中的影响。在三对CML细胞系以及CML患者的外周血单个核细胞（PBMC）中检测了六种α-2,8-唾液酸转移酶的表达谱。细胞多药耐药表型与ST8SIA4和ST8SIA6水平呈正相关。此外，ST8SIA4介导磷脂酰肌醇-3激酶（PI3K）/Akt信号通路的活性以及P-糖蛋白（P-gp）的表达。用其特异性抑制剂LY294002靶向PI3K/Akt通路，或通过Akt RNA干扰可逆转K562/ADR细胞的多药耐药表型。抑制PI3K/Akt通路也减弱了ST8SIA4过表达对多药耐药的影响。因此，本研究表明α-2,8-唾液酸转移酶可能通过ST8SIA4调节PI3K/Akt信号活性和P-gp的表达参与CML细胞多药耐药性的发展。
