通过Wnt/β-连环蛋白信号通路,干预 KRT17 反转三阴性乳腺癌细胞对阿霉素的耐药性。
Interference KRT17 reverses doxorubicin resistance in triple-negative breast cancer cells by Wnt/β-catenin signaling pathway.
发表日期:2023 Aug 27
作者:
Liqiong Wu, Wenshuang Ding, Xiaopai Wang, Xiubo Li, Jing Yang
来源:
Genes & genomics
摘要:
三阴性乳腺癌(TNBC)是乳腺癌的亚型之一,具有最高的恶性程度,并且由于缺乏激素受体而容易对药物产生抗性。对TNBC抗药机制的研究尤为重要。角蛋白17(KRT17)在TNBC中高度表达。类蒽环类染料阿霉素(Dox)是早期三阴性乳腺癌常用的化疗药物。本研究调查了KRT17在TNBC-Dox抗药性中的作用。采用免疫组化染色、qPCR、蛋白免疫印迹和免疫荧光等方法检测TNBC-Dox抗药性患者以及TNBC-Dox抗药性MDA-MB-468和MDA-MB-231中KRT17的表达。采用CCK8、克隆形成、Transwell侵袭和划痕愈合实验来确定KRT17在抑制TNBC-Dox抗药性细胞增殖和迁移中的作用。KRT17在TNBC-Dox抗药性细胞中高度表达。KRT17的敲减显著减少了TNBC-Dox抗药性和父细胞系的IC50,并且降低了TNBC-Dox抗药性细胞株的增殖和侵袭能力。KRT17调节Wnt/β-连环蛋白信号通路。Wnt信号通路的活化剂逆转了KRT17敲减对TNBC-Dox抗药性细胞增殖和迁移的抑制作用。KRT17能够抑制Wnt/β-连环蛋白信号通路,从而减少TNBC-Dox抗药性细胞的增殖和侵袭能力。©2023年。作者。
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.This study investigated the role of KRT17 in TNBC-Dox resistance.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.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.KRT17 can inhibit the Wnt/β-catenin signaling pathway, thereby reducing the proliferation and invasion ability of TNBC-Dox-resistant cells.© 2023. The Author(s).