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Overexpression of NDRG2 promotes the therapeutic effect of pazopanib on ovarian cancer
Journal of Receptors and Signal Transduction ( IF 2.8 ) Pub Date : 2020-10-13 , DOI: 10.1080/10799893.2020.1831536
Ying Cui 1 , Guihua Shen 1 , Linlin Ma 1 , Qiubo Lv 1
Affiliation  

Abstract

Objectives

Ovarian cancer is the second commonly seen cancer in the US, patients with ovarian cancer are commonly diagnosed in the advanced stage. Pazopanib is an inhibitor of multiple tyrosine kinases and has been approved in treatment for carcinoma by FDA. N-myc downstream-regulated gene 2 (NDRG2) has been regarded as a cancer suppressor gene and presented an inhibition effect in cancer proliferation, invasion, and migration.

Design: NDRG2 was overexpressed or inhibited in SKOV-3 cells, then experiments were performed to detect the apoptosis of cells. The expression or secretion of pro-cancer molecules was detected. And the expression of apoptosis-related proteins and the ASK1/JNK1 signaling pathway was detected.

Methods

The NDRG2 overexpression and inhibition model was firstly constructed in SKOV-3 cells, the apoptotic cells were detected using flow cytometry. The expression of cellular metastasis genes was detected using the qPCR method. The angiogenesis factors was detected using the ELISA method. Expression of each target protein was detected using western blotting analysis.

Results

NDRG2 overexpression and inhibition model were constructed in the SKOV-3 cell line, overexpression of NDRG2 enhanced the effect of pazopanib on inhibition of the expression of metastasis-related molecules and angiogenesis-related factors. The apoptosis process of cells was also enhanced after overexpression of NDRG2, and these effects were regulated by the activation of the ASK1/JNK1 signaling pathway.

Limitations: The effect of NDRG2 in animal models and more cell lines needs to be explored in further study.

Conclusions

NDRG2 might be a therapeutic target in treatment for ovarian cancer.



中文翻译:

NDRG2过表达促进帕唑帕尼对卵巢癌的治疗作用

摘要

目标

卵巢癌是美国第二常见的癌症,卵巢癌患者通常被诊断为晚期。帕唑帕尼是多种酪氨酸激酶的抑制剂,已被 FDA 批准用于治疗癌症。N-myc 下游调节基因 2 (NDRG2) 被认为是一种抑癌基因,在癌症的增殖、侵袭和迁移中具有抑制作用。

设计: NDRG2在SKOV-3细胞中过表达或被抑制,然后进行实验检测细胞的凋亡。检测了促癌分子的表达或分泌。并检测凋亡相关蛋白和ASK1/JNK1信号通路的表达。

方法

首次在SKOV-3细胞中构建NDRG2过表达抑制模型,采用流式细胞仪检测凋亡细胞。使用qPCR方法检测细胞转移基因的表达。使用ELISA方法检测血管生成因子。使用蛋白质印迹分析检测每种靶蛋白的表达。

结果

在SKOV-3细胞系中构建了NDRG2过表达和抑制模型,NDRG2过表达增强了帕唑帕尼抑制转移相关分子和血管生成相关因子表达的作用。过表达 NDRG2 后,细胞的凋亡过程也得到了增强,这些作用受 ASK1/JNK1 信号通路的激活的调节。

局限性: NDRG2 在动物模型和更多细胞系中的作用需要进一步研究。

结论

NDRG2 可能是治疗卵巢癌的治疗靶点。

更新日期:2020-10-13
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