KB-8-5-11 耐药癌细胞对顺铂的交叉敏感性。

Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.

机构信息

Department of Histopathology, Trinity College Dublin, 1.18 Sir Patrick Dun Research Laboratory, Central Pathology Building, St James' Hospital, Dublin 8, Ireland.

出版信息

Anticancer Res. 2014 Jan;34(1):503-7.

PMID:24403508

Abstract

BACKGROUND

KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer.

MATERIALS AND METHODS

A Taqman low-density array was used to characterize the expression of 380 genes previously associated with chemoresistance. Identified pathways were further analyzed using cytotoxicity assays, metabolomics and western blots.

RESULTS

KB-8-5-11 cells were sensitive to CuSO4 and the glutathione inhibitor buthionine sulphoximine. Expression of ATPase, Cu(2+) transporting alpha (ATP7A) and ATP7B were decreased at the protein and gene levels respectively in KB-8-5-11. KB-8-5-11 had decreased gene expression of glutathione S-transferase pi 1 (GSTP1), GSTA4 and GSTK1. Cisplatin treatment significantly lowered total cellular glutathione in parental KB-3-1 cells. Glutathione also tended to be lower in KB-8-5-11 cells compared to KB-3-1 cells.

CONCLUSION

KB-8-5-11 cells have alterations in their copper transporters and glutathione metabolism, contributing to their cisplatin-sensitive phenotype.

摘要

背景

KB-8-5-11 细胞是一种耐药性宫颈细胞模型，过度表达 ABCB1（P-糖蛋白）。KB-8-5-11 对非 ABCB1 底物顺铂变得敏感。了解顺铂的协同敏感性机制可能会导致癌症患者对铂类药物敏感性的生物标志物的发现。

材料与方法

使用 Taqman 低密度阵列来描述与化疗耐药性相关的 380 个基因的表达。使用细胞毒性测定、代谢组学和 Western blot 进一步分析鉴定出的途径。

结果

KB-8-5-11 细胞对 CuSO4 和谷胱甘肽抑制剂丁硫氨酸亚砜胺敏感。KB-8-5-11 中的 ATP 酶、Cu(2+) 转运体 alpha (ATP7A) 和 ATP7B 的蛋白和基因水平表达均降低。KB-8-5-11 的谷胱甘肽 S-转移酶 pi 1 (GSTP1)、GSTA4 和 GSTK1 的基因表达降低。顺铂处理显著降低亲本 KB-3-1 细胞中的总细胞谷胱甘肽。与 KB-3-1 细胞相比，KB-8-5-11 细胞中的谷胱甘肽也较低。