Effect of tumor suppressor gene PTEN on the resistance to cisplatin in human ovarian cancer cell lines and related mechanisms
Effect of tumor suppressor gene PTEN on the resistance to cisplatin in human ovarian cancer cell lines and related mechanisms
复制标题
抑癌基因PTEN对人卵巢癌细胞系顺铂耐药的影响及相关机制
DOI：
10.1016/j.canlet.2008.06.012
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发表时间：
2008-11-28
期刊：
影响因子：
9.7
通讯作者：
Ma, Ding
中科院分区：
文献类型：
--
作者：
Wu, HuiJuan;Cao, Yang;Ma, Ding
目的 探讨PTEN基因在人卵巢癌细胞顺铂化疗敏感性中的作用及相关机制。方法构建PTEN靶向短发夹RNA（shRNA）表达载体和野生型正义PTEN质粒，分别转染PTEN shRNA或野生型PTEN质粒转染人卵巢顺铂敏感癌细胞系OV2008及其耐药变种C13*细胞，然后用顺铂。接下来，分别在 OV2008/PTENshRNA 细胞或 C13*/p-PTEN 细胞中共转染反义或正义 AKT 质粒来调节 AKT 活性。评价转染上述载体对细胞生长、凋亡以及PTEN和AKT表达的影响。结果OV2008细胞中PTEN表达显着高于C13*细胞。将PTEN shRNA转染至OV2008细胞中，PTEN表达显着下调，磷酸AKT蛋白表达上调，转染细胞对顺铂产生耐药性。有义PTEN转染过表达PTEN可明显增强顺铂诱导的C13*细胞凋亡。此外，AKT 活性降低可增加顺铂诱导的 OV2008/PTENshRNA 细胞凋亡。将pcDNA3.1-AKT质粒转染C13*/p-PTEN细胞后，AKT活性增强，顺铂诱导的细胞凋亡受到显着抑制。 结论 PTEN可能通过灭活PI3K/AKT细胞生存途径，逆转人卵巢癌细胞对顺铂的化疗耐药性，可能作为治疗化疗耐药性卵巢癌的潜在分子靶点。 (c) 2008 Elsevier Ireland Ltd. 保留所有权利。
Purpose The aim of this study was to explore role of PTEN gene in chemosensitivity to cisplatin in human ovarian cancer cells and related mechanisms.Method A PTEN-targeted short hairpin RNA (shRNA) expression vector and a wild-type sense PTEN plasmid were constructed, human ovarian cisplatin-sensitive cancer cell line OV2008 and its resistant variant C13* cells were transfected with PTEN shRNA or wild-type PTEN plasmid, respectively, and cells were then treated with cisplatin. Next, AKT activity was regulated with co-transfection of antisense or sense AKT plasmid in OV2008/PTENshRNA cells or C13*/p-PTEN cells, respectively. Effects of transfection of above vectors on cell growth, apoptosis and expression of PTEN and AKT were evaluated.Results Expression of PTEN in OV2008 cells was significantly higher than that in C13* cells. Transfection of PTEN shRNA into OV2008 cells remarkably down-regulated expression of PTEN and up-regulated expression of phospho-AKT protein, with transfected cells being resistant to cisplatin. Overexpression of PTEN by transfection with sense PTEN obviously enhanced cisplatin-induced apoptosis of C13* cells. Furthermore, decreased AKT activity could increase cisplatin-induced apoptosis in OV2008/PTENshRNA cells; while, transfection of pcDNA3.1-AKT plasmid into C13*/p-PTEN cells resulted in increased activity of AKT, with cisplatin-induced apoptosis being inhibited significantly.Conclusions PTEN might reverse chemoresistance to cisplatin in human ovarian cancer cells through inactivation of the PI3K/AKT cell survival pathway and may serve as a potential molecular target for the treatment of chemoresistant ovarian cancer. (c) 2008 Elsevier Ireland Ltd. All rights reserved.