干扰KRT17通过Wnt/β-catenin信号通路逆转三阴性乳腺癌细胞中的阿霉素耐药性,Genes & Genomics

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干扰KRT17通过Wnt/β-catenin信号通路逆转三阴性乳腺癌细胞中的阿霉素耐药性
Genes & Genomics ( IF 1.6 ) Pub Date : 2023-08-27 , DOI: 10.1007/s13258-023-01437-y
Liqiong Wu _{1,

2} , Wenshuang Ding _{1,

2} , Xiaopai Wang _{1,

2} , Xiubo Li _{1,

2} , Jing Yang _{1,

2}

Affiliation

背景

三阴性乳腺癌（TNBC）是乳腺癌中恶性程度最高的亚型，由于缺乏激素受体而容易产生耐药性。TNBC耐药机制的研究尤为重要。角蛋白 17 (KRT17) 在 TNBC 中高度表达。蒽环类阿霉素（Dox）是早期三阴性乳腺癌常用的化疗药物。

客观的

本研究调查了 KRT17 在 TNBC-Dox 耐药性中的作用。

方法

采用免疫组织化学染色、qPCR、蛋白质印迹（WB）和免疫荧光检测TNBC-Dox耐药患者以及TNBC-Dox耐药MDA-MB-468和MDA-MB-231中KRT17的表达。通过CCK8、克隆形成、Transwell侵袭和伤口愈合实验来确定KRT17敲低TNBC-Dox抗性细胞中KRT17对增殖和迁移的影响。

结果

KRT17 在 TNBC-Dox 耐药细胞中高表达。KRT17的敲低显着降低了TNBC-Dox耐药细胞系和亲本菌株的IC50，并且还降低了TNBC-Dox耐药细胞系的增殖和侵袭能力。KRT17 调节 Wnt/β-catenin 信号通路。KRT17 敲低对 TNBC-Dox 耐药细胞增殖和迁移的抑制作用可被 Wnt 信号通路激活剂逆转。

结论

KRT17可以抑制Wnt/β-catenin信号通路，从而降低TNBC-Dox耐药细胞的增殖和侵袭能力。

"点击查看英文标题和摘要"

Interference KRT17 reverses doxorubicin resistance in triple-negative breast cancer cells by Wnt/β-catenin signaling pathway

Background

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with the highest degree of malignancy and is easily resistant to drugs due to the lack of hormone receptors. Research on the resistance mechanisms in TNBC is particularly important. Keratin 17 (KRT17) is highly expressed in TNBC. Anthracycline doxorubicin (Dox) is a commonly used chemotherapeutic drug for early stage triple-negative breast cancer.

Objective

This study investigated the role of KRT17 in TNBC-Dox resistance.

Methods

Immuno-histochemical staining, qPCR, western blotting (WB), and immunofluorescence were used to detect the expression of KRT17 in TNBC-Dox-resistant patients and in TNBC-Dox-resistant MDA-MB-468 and MDA-MB-231. the effect of KRT17 on the proliferation and migration in KRT17 knockdown of TNBC-Dox-resistant cells was determined by the CCK8, clone formation, transwell invasion and wound healing assays were used to determine.

Results

KRT17 was highly expressed in the TNBC-Dox-resistant cells. Knockdown of KRT17 significantly reduced the IC50s of TNBC-Dox-resistant and parental strains and also reduced the proliferation and invasion abilities of TNBC-Dox-resistant cell lines. KRT17 regulated the Wnt/β-catenin signaling pathway. The inhibitory effect of KRT17 knockdown on the proliferation and migration of TNBC-Dox-resistant cells was reversed by an activator of the Wnt signaling pathway.