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沉默赖氨酰氧化酶样蛋白2通过整合素β1减弱喉癌中癌症干细胞样特性和顺铂耐药性。

Silencing PLOD2 attenuates cancer stem cell-like characteristics and cisplatin-resistant through Integrin β1 in laryngeal cancer.

作者信息

Song Meiyan, Liu Xing, Li Tao, Zhang Yueqin, Zhao Xiaoyan, Sun Wen, Li Zhen

机构信息

Yantaishan Hospital, Yantai, Shandong, China.

Department of Otolaryngology, Qingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser Hospital), Qingdao, Shandong, China.

出版信息

Transl Oncol. 2022 Aug;22:101460. doi: 10.1016/j.tranon.2022.101460. Epub 2022 Jun 3.

Abstract

Laryngeal cancer (LC) is an aggressive malignancy resistant to drug treatments. It has been postulated that cancer stem cells (CSCs) persist in a unique population of cancer cells involved in tumor progression and drug-resistance. In the present study, the effects of PLOD2 expression on ordinary and Cisplatin (DDP)-resistance (R) cells were investigated in TU686 and TU138 cells and Xenograft model. Cell viability, invasion and cell apoptosis, CD44 and CD133 expressions, MRP1 and P-gp expressions were measured by CCK-8 assay, Transwell, flow cytometry, immunofluorescence and Western blotting respectively. The results of our study demonstrated that suppressing the expression of PLOD2 could meditate LC stem cell-like features by decrease cell viability and invasion, increase apoptotic rate, decrease CD44 and CD133 expressions via Integrin β1. Meanwhile, the inhibition of PLOD2 expression could decrease P-gp and MRP1expression thus markedly regulate DDP-R LC cells stemness and drug-resistance via Integrin β1. Our findings provided a new rationale for subsequent academic and clinical research on LC drug-resistance.

摘要

喉癌(LC)是一种对药物治疗具有抗性的侵袭性恶性肿瘤。据推测,癌症干细胞(CSCs)存在于参与肿瘤进展和耐药性的独特癌细胞群体中。在本研究中,在TU686和TU138细胞以及异种移植模型中研究了PLOD2表达对普通和顺铂(DDP)耐药(R)细胞的影响。分别通过CCK-8测定、Transwell、流式细胞术、免疫荧光和蛋白质印迹法测量细胞活力、侵袭和细胞凋亡、CD44和CD133表达、MRP1和P-糖蛋白表达。我们的研究结果表明,抑制PLOD2的表达可通过降低细胞活力和侵袭、增加凋亡率、通过整合素β1降低CD44和CD133表达来介导LC干细胞样特征。同时,抑制PLOD2表达可降低P-糖蛋白和MRP1表达,从而通过整合素β1显著调节DDP-R LC细胞的干性和耐药性。我们的研究结果为后续关于LC耐药性的学术和临床研究提供了新的理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e566/9168686/9d71b1d745d7/gr1.jpg

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