高迁移率族蛋白 B1 促进非小细胞肺癌的恶性进展并导致顺铂耐药。
Elevated HMGB1 promotes the malignant progression and contributes to cisplatin resistance of non-small cell lung cancer.
机构信息
Department of Thoracic Surgery, Affiliated People's Hospital of Inner Mongolia Medical University, No.1 Tong Dao Bei Road, Hohhot, 010059, China.
Inner Mongolia Cancer Hospital and Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, 010020, China.
出版信息
Hereditas. 2023 Jul 31;160(1):33. doi: 10.1186/s41065-023-00294-9.
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.
背景
高迁移率族蛋白 B-1（HMGB1）在肿瘤发生和发展中具有关键作用，包括肺癌。然而，非小细胞肺癌（NSCLC）中更多的 HMGB1 相关细节仍在很大程度上不清楚。
方法
通过 ELISA 测定恶性（MPE）和非恶性胸腔积液（BPE）中的 HMGB1 和炎症因子。此外，通过 qRT-PCR、western blot 或免疫组化检测 NSCLC A549、A549-DDP 细胞系和异种移植模型中 HMGB1、耐药和凋亡蛋白的表达。分别通过 MTT、Transwell 和流式细胞术测定细胞活力、迁移/侵袭和凋亡。
结果
MPE 中的炎症因子和 HMGB1 表达明显高于 NSCLC 的 BPE。与术前和相邻组织相比，复发性组织中 HMGB1、耐药蛋白和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、增殖性和耐药性特征。当干扰 HMGB1 时，相关能力会被逆转。过表达的 HMGB1 在异种移植模型中与细胞质中的耐药蛋白 P-gp 表现出相似的共定位，而低 HMGB1 表达定位于细胞核。
结论
HMGB1 过表达显著促进了 NSCLC 体内外的恶性进展和顺铂耐药性。
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