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

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.

• Authors: Ying Ma, Qin Feng, Bateer Han, Rong Yu, Zhiyong Jin
• Journal: Hereditas (Hereditas) Vol. 160 Issue 1 Pg. 33 (Jul 31 2023) ISSN: 1601-5223 [Electronic] England
• PMID: 37518006 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Cisplatin
• HMGB1 Protein
• MicroRNAs
• HMGB1 protein, human

Topics

• Humans
• Apoptosis
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Cell Line, Tumor
• Cisplatin (pharmacology, therapeutic use)
• Drug Resistance, Neoplasm (genetics)
• HMGB1 Protein (genetics, metabolism)
• Lung Neoplasms (drug therapy, genetics)
• MicroRNAs (metabolism)
• Animals