Elevated HMGB1 promotes the malignant progression and contributes to cisplatin resistance of non-small cell lung cancer.

IF 2.7 3区生物学

Hereditas Pub Date : 2023-07-31 DOI:10.1186/s41065-023-00294-9

Ying Ma, Qin Feng, Bateer Han, Rong Yu, Zhiyong Jin

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引用次数: 0

Abstract

Background: HMGB1 (high mobility group box B-1) exhibits crucial role in tumor genesis and development, including lung cancer. Whereas, more HMGB1-related details in non-small cell lung cancer (NSCLC) are still largely unclear.

Methods: The HMGB1 and inflammatory factors in malignant (MPE) and non-malignant pleural effusion (BPE) were determined by ELISA. Additionally, qRT-PCR, western blot, or immunohistochemistry were used to determine HMGB1, drug-resistant and apoptotic proteins' expressions in NSCLC A549, A549-DDP cell lines, and xenograft model. Cell viability, migration/ invasion, and apoptosis were analyzed using MTT, Transwell, and flow cytometry assays, respectively.

Results: Inflammatory factors and HMGB1 expressions in MPE were significantly higher than BPE of NSCLC. Compared with preoperative and adjacent tissues, significantly higher HMGB1, drug-resistant protein, and anti-apoptotic protein expressions were observed in recurrent tissues. Overexpressed HMGB1 induced NSCLC cells to exhibit stronger aggressive, proliferative, and drug-resistant features. The related abilities were reversed when HMGB1 was interfered. Overexpressed HMGB1 showed a similar co-localization with drug resistant protein P-gp in cytoplasm in xenograft model, while low HMGB1 expression localized in cell nucleus.

Conclusions: HMGB1 overexpression significantly promoted the malignant progression and cisplatin resistance of NSCLC in vitro and in vivo.

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HMGB1升高促进非小细胞肺癌的恶性进展，促进顺铂耐药。

背景:HMGB1(高迁移率组框B-1)在包括肺癌在内的肿瘤发生发展中发挥重要作用。然而，非小细胞肺癌(NSCLC)中更多hmgb1相关细节仍不清楚。方法:采用酶联免疫吸附法(ELISA)检测恶性胸腔积液(MPE)和非恶性胸腔积液(BPE)中HMGB1及炎症因子水平。此外，采用qRT-PCR、western blot或免疫组化检测HMGB1、耐药蛋白和凋亡蛋白在NSCLC A549、A549- ddp细胞系和异种移植模型中的表达。分别采用MTT、Transwell和流式细胞术分析细胞活力、迁移/侵袭和凋亡。结果:炎症因子及HMGB1在MPE中的表达明显高于NSCLC的BPE。与术前及邻近组织比较，复发组织中HMGB1、耐药蛋白、抗凋亡蛋白的表达明显升高。过表达HMGB1诱导NSCLC细胞表现出更强的侵袭性、增殖性和耐药特征。当HMGB1受到干扰时，相关能力发生逆转。在异种移植物模型中，HMGB1过表达与耐药蛋白P-gp在细胞质中表现出相似的共定位，而HMGB1低表达定位于细胞核。结论:HMGB1过表达在体外和体内均可显著促进NSCLC的恶性进展和顺铂耐药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.