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蛋白酪氨酸磷酸酶PRL-3是近年发现的蛋白酪氨酸磷酸酶家族成员,能促进肿瘤细胞的侵袭、转移及上皮细胞间质转型,提示PRL-3可能在肿瘤发生发展及诱导肿瘤干细胞生成中发挥重要作用.由于侧群(SP)细胞具有许多干细胞的性质,SP细胞分选是目前筛选和分离获得干细胞或前体细胞常用的有效方法.为探讨PRL-3在诱导干细胞生成中的潜在作用,本文在建立过表达PRL-3的人胃癌细胞BGC823的基础上,通过SP分选和CCK-8的方法分析PRL-3对BGC823细胞中SP细胞的比例以及对化疗药物耐受性的影响.结果提示,高表达PRL-3提高BGC823中SP细胞的比例(2.5%vs 9.4%),同时增加BGC823对化疗药物紫杉醇和顺铂的耐受性(相对于对照细胞,其耐药指数分别为1.75和1.29).由于SP细胞的产生和细胞耐药性的提高与ABC家族基因表达水平上调密切相关,通过定量RT-PCR和Western印迹检测发现,PRL-3能上调ABCB1和ABCG2的表达.上述研究结果表明,PRL-3有可能通过上调ABCB1和ABCG2的表达,增加胃癌细胞BGC823的SP细胞比例并增加其对化疗药物的耐受性.
Protein tyrosine phosphatase PRL-3 is a member of the protein tyrosine phosphatase family found in recent years, can promote tumor cell invasion, metastasis and epithelial cell stromal transformation, suggesting that PRL-3 may be in tumor development and induction of tumor stem cells (SP) cells have many stem cell properties, SP cell sorting is currently available screening and isolation of stem cells or precursor cells commonly used effective method to explore the PRL-3 in the induction of stem cell generation In this study, based on the establishment of human gastric cancer cell line BGC823 overexpressing PRL-3, the ratio of PRL-3 to SP cells in BGC823 cells and the tolerance to chemotherapeutics were analyzed by SP sorting and CCK-8 The results suggest that high expression of PRL-3 increases the proportion of SP cells in BGC823 (2.5% vs 9.4%), while increasing the tolerance of BGC823 to chemotherapeutic drugs paclitaxel and cisplatin (relative to control cells, respectively, the resistance index Was 1.75 and 1.29) .Because the generation of SP cells and the increase of cell resistance were closely related to the up-regulation of ABC family gene expression, PRL-3 could up-regulate the expression of ABCB1 and ABCG2 by quantitative RT-PCR and Western blotting The above results show that, PRL-3 is possible through regulated expression of ABCB1 and ABCG2, increase the proportion of SP cells and gastric cancer cells BGC823 increase its resistance to chemotherapeutic drugs.