中国临床药理学杂志2026，Vol.42Issue(14)：1997-2003,7.DOI:10.13699/j.cnki.1001-6821.2026.14.008
纳布啡通过HMGB1-RAGE信号通路抑制肺癌细胞恶性生物学行为的研究
Research on the inhibition of malignant biological behaviors of lung cancer cells by nalbuphine by HMGB1-RAGE signaling pathway
摘要
Abstract
Objective To investigate whether nalbuphine can influence the development of lung cancer(LC)through the high mobility group box 1 protein(HMGB1)-receptor for advanced glycation end products(RAGE)signaling pathway and to explore its specific mechanisms.Methods Human LC A549 cells were cultured in vitro,and the cytotoxicity of nalbuphine on A549 cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.A549 cells were divided into the following groups:control group,experimental low-dose group,experimental high-dose group,pcDNA-NC group and nalbuphinepcDNA-HMGB1 group.Cell proliferation,migration and invasion were evaluated using cell counting kit-8(CCK-8)assay,colony formation assay,wound healing assay and Transwell invasion assay.The mRNA expression levels of HMGB1 and RAGE were detected by quantitative real-time polymerase chain reaction(qRT-PCR).The protein expression levels of cyclin-dependent kinase 4(CDK4),matrix metalloproteinase 2(MMP-2),E-cadherin,N-cadherin and HMGB1-RAGE signaling pathway-related proteins were detected by Western blot.Results The cell survival rates of the normal group,low-dose experimental group,high-dose experimental group,pcDNA-NC group and pcDNA-HMGB1 group were(100.00±0)％,(74.58±7.88)％,(52.37±5.97)％,(56.34±6.01)％and(87.26±9.21)％,respectively;the numbers of colonies formed were(189.17±19.35),(105.83±8.13),(83.33±8.66),(90.83±9.64)and(162.50±16.87)cells,respectively;the numbers of invading cells were(129.17±13.24),(75.50±7.99),(55.83±6.27),(54.17±5.95)and(102.50±10.97)cells,respectively;the relative expression levels of HMGB1 mRNA were 1.00±0,0.75±0.08,0.52±0.05,0.56±0.06 and 0.87±0.09,respectively;the relative expression levels of RAGE mRNA were 1.00±0,0.66±0.07,0.47±0.05,0.48±0.05 and 0.92±0.09,respectively;the relative expression levels of CDK4 protein were 1.09±0.10,0.53±0.05,0.24±0.02,0.29±0.03 and 0.79±0.08,respectively;the relative expression levels of MMP-2 protein were 1.17±0.12,0.67±0.07,0.34±0.04,0.40±0.04 and 0.86±0.09,respectively;the relative expression levels of E-cadherin protein were 0.74±0.08,1.26±0.13,1.49±0.15,1.42±0.14 and 0.94±0.09,respectively;the relative expression levels of N-cadherin protein were 0.98±0.10,0.72±0.07,0.51±0.05,0.53±0.05 and 0.89±0.09,respectively.Compared the normal group with the low-dose and high-dose experimental groups,compared the high-dose experimental group with low-dose experimental group,compared pcDNA-HMGB1 group with pcDNA-NC group,the above indicators showed statistically significant differences(all P＜0.05).Conclusion Nalbuphine inhibits LC cell proliferation,migration,and invasion by suppressing the activation of the HMGB1-RAGE signaling pathway.关键词
纳布啡/高迁移率族蛋白B1-晚期糖基化终末产物受体信号通路/肺癌/增殖/迁移/侵袭Key words
nalbuphine/high mobility group box 1 protein-receptor for advanced glycation end products signaling pathway/lung cancer/proliferation/migration/invasion分类
医药卫生引用本文复制引用
贺丽艳,师婷婷..纳布啡通过HMGB1-RAGE信号通路抑制肺癌细胞恶性生物学行为的研究[J].中国临床药理学杂志,2026,42(14):1997-2003,7.基金项目
河北省中医药类科学研究课题计划项目基金资助项目(2025614) （2025614）
