Centre for Cell Chromosome Biology, Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge UB8 3PH, UK.
Anticancer Res. 2010 Sep;30(9):3529-34.
BACKGROUND/AIM: A limitation to successful cancer chemotherapy treatments is the acquisition of drug resistance. In advanced-stage ovarian cancer, the mammalian target of rapamycin (mTOR) pathway is up-regulated, and inhibition of this pathway increases chemosensitivity in ovarian carcinoma cell lines. In this study, the expression of DEPTOR, mTOR, RICTOR, RAPTOR and S6 kinases were investigated in SKOV-3 and PEO1 parental and the paclitaxel-resistant (TaxR) SKOV-3TaxR and PEO1TaxR cell lines.
RT-PCR, immunofluorescent analysis and Western blotting were carried out.
Quantitative RT-PCR revealed significant up-regulation of DEPTOR in both paclitaxel-resistant cell lines. SKOV-3TaxR exhibited down-regulation of RICTOR, RAPTOR and mTOR, whereas PEO1-TaxR showed down-regulation of RAPTOR and up-regulation of RICTOR and mTOR. Semi-quantitative RT-PCR analysis revealed marked changes in the expression of p70S6K splice variants mRNA in PEO1TaxR. Moreover, the phosphorylation status of p70S6K at Ser371 appears to be cell-type specific.
We hypothesize that mTOR signalling may play a role in mediating paclitaxel resistance in ovarian cancer.
背景/目的：癌症化疗治疗成功的一个限制因素是获得耐药性。在晚期卵巢癌中，雷帕霉素靶蛋白（mTOR）途径被上调，抑制该途径可增加卵巢癌细胞系的化疗敏感性。在这项研究中，研究了 DEPTOR、mTOR、RICTOR、RAPTOR 和 S6 激酶在 SKOV-3 和 PEO1 亲本以及紫杉醇耐药（TaxR）SKOV-3TaxR 和 PEO1TaxR 细胞系中的表达。
进行了 RT-PCR、免疫荧光分析和 Western blot 分析。
定量 RT-PCR 显示紫杉醇耐药细胞系中 DEPTOR 的表达显著上调。SKOV-3TaxR 表现出 RICTOR、RAPTOR 和 mTOR 的下调，而 PEO1TaxR 则表现出 RAPTOR 的下调和 RICTOR 和 mTOR 的上调。半定量 RT-PCR 分析显示 PEO1TaxR 中 p70S6K 剪接变体 mRNA 的表达发生了显著变化。此外，p70S6K 在 Ser371 处的磷酸化状态似乎具有细胞类型特异性。
我们假设 mTOR 信号通路可能在介导卵巢癌对紫杉醇的耐药性中发挥作用。
