CIP2A 表达增加与胃癌对顺铂化疗耐药相关。

Increase in CIP2A expression is associated with cisplatin chemoresistance in gastric cancer.

机构信息

Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.

School of Biomedical Engineering, Hubei University of Medicine, Shiyan, Hubei 442000, China.

出版信息

Cancer Biomark. 2018 Feb 6;21(2):307-316. doi: 10.3233/CBM-170416.

DOI:10.3233/CBM-170416

PMID:29103022

Abstract

BACKGROUND

The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which involves in the progression of several human malignancies. Development of cisplatin (DDP) resistance is the obstacle to an effective control of gastric cancer (GC) clinically.

OBJECTIVE

We thus assessed whether CIP2A expression is associated with sensitivity of GC to DDP.

METHODS

Real-time quantitative PCR, immunohistochemical analysis, or western blotting was performed to detect CIP2A expression in GC patients' tissues. SGC7901/DDP cells were transfected with CIP2A siRNA. MTT assay was used to determine the DDP-sensitivity of cells. Flow cytometry was used to measure cell apoptosis.

RESULTS

CIP2A has higher expression in DDP-resistant GC patients. DDP-resistant GC patients with high CIP2A expression presented with poorer overall survival rates than those with low CIP2A expression. CIP2A knockdown in DDP-resistant GC cells resulted in attenuated proliferative abilities and increased apoptosis level. CIP2A depletion sensitizes DDP-resistant cells to DDP and CIP2A overexpression antagonizes DDP-sensitive cells to DDP. CIP2A influences the expression of multidrug resistance-related proteins in GC cells.

CONCLUSIONS

Our results suggested that CIP2A oncoprotein plays an important role in DDP resistance of GC and could serve as a novel therapeutic target for the treatment of GC patients with DDP resistance.

摘要

背景

蛋白磷酸酶 2A 的致癌抑制剂（CIP2A）是一种癌蛋白，参与多种人类恶性肿瘤的进展。顺铂（DDP）耐药的发展是临床上有效控制胃癌（GC）的障碍。

目的

因此，我们评估了 CIP2A 的表达是否与 GC 对 DDP 的敏感性相关。

方法

实时定量 PCR、免疫组织化学分析或 Western blot 检测 GC 患者组织中的 CIP2A 表达。用 CIP2A siRNA 转染 SGC7901/DDP 细胞。MTT 法测定细胞对 DDP 的敏感性。流式细胞术检测细胞凋亡。

结果

CIP2A 在 DDP 耐药的 GC 患者中表达较高。CIP2A 高表达的 DDP 耐药 GC 患者总生存率低于 CIP2A 低表达的患者。DDP 耐药 GC 细胞中 CIP2A 的敲低导致增殖能力减弱和凋亡水平增加。CIP2A 耗竭使 DDP 耐药细胞对 DDP 敏感，CIP2A 过表达使 DDP 敏感细胞对 DDP 耐药。CIP2A 影响 GC 细胞中多药耐药相关蛋白的表达。