酪氨酸磷酸酶PRL-3增加人胃癌细胞BGC823的SP细胞比例并提高其对化疗药物的耐受性  

PRL-3 Increases Side Population in Human Gastric Cancer BGC823 Cells and Elevates Resistance to Chemotherapeutic Drugs

作　　者：宋倩[1] 孟麟[1] 曲立科[1] 廉沈沂[1] 寿成超[1] 

机构地区：[1]北京大学肿瘤医院生物化学与分子生物学研究室,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《中国生物化学与分子生物学报》2013年第3期257-263,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81071732,30973407)资助~~

摘　　要：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.PRL-3 （phosphatase of regenerating liver-3） , a metastasis-associated protein, belongs to the PRL family of protein tyrosine phosphatases. Recent studies showed that PRL-3 plays a stimulatory role in triggering the epithelial-mesenchymal transitions （EMT） during cancer metastasis, suggesting that PRL-3 may be essential for tumorigenesis and induction of tumor stem cells. As side population （SP） cells exhibit several stem cell-like properties, SP isolation is a valuable approach to obtain and identify cancer stem cells. To study the potential effect of PRL-3 on tumor stem cells, flow cytometry and CCK-8 assay were utilized to analyze the ratio of SP ceils in cancer ceils. The resistance to chemotherapeutic drugs in BGC823 cells stably expressing PRL-3 （823-P） was also examined. The results showed that PRL.3 increases the ratio of SP cells from 2.5% to 9.4% , and confers resistance to Taxol and Cisplatin （resistance index of 1.75 and 1.29, respectively）. Since the generation of SP cells and resistance to chemotherapeutic drugs are closely related to ABC （ATP-binding cassette） family, quantitative RT-PCRand Western blotting were performed to check the expression of ABC transporters. We found that PRL-3 up-regulated ABCB1 and ABCG2 expression. Therefore, PRL-3 may promote SP cells in cancer cell lines and increase resistance to chemotherapeutic drugs through elevated ABCB1 and ABCG2 expression.

关 键 词：PRL-3 侧群细胞 ABC家族 

分 类 号：Q5-33[生物学—生物化学]