Abstract:Objective: To investigate the effect of phloretin on the CC chemokine ligand 2 (CCL2) - CC chemokine receptor 2 (CCR2) signaling axis on the malignant progression of lung cancer cells. Methods: A549 cells were grouped into a control group (untreated A549 cells), a low-dose phloretin group (500 μmoL/L phloretin treated A549 cells), a medium-dose phloretin group (750μmoL/L phloretin treated A549 cells), a high-dose phloretin group (1000μmoL/L phloretin treated A549 cells), and a high-dose phloretin+GW0742 group (1000μmoL/L phloretin and 1.0μmoL/L CCL2-CCR2 signaling pathway activator GW0742 co-treated A549 cells). CCK-8 method and flow cytometry were applied to detect A549 cell proliferation and apoptosis, respectively; the Transwell method was applied to detect cell migration and invasion; Western blot was applied to determine the expression of CCL2-CCR2 signaling axis-related proteins. Results: The OD450 value, migration and invasion numbers, and the CCL2, CCR2 protein expression in the low, medium, and high dose phloretin groups were lower than those in the control group (P<0.05), the apoptosis rate of cells was higher (P<0.05), in a dose-dependent manner. The OD450 value, migration and invasion numbers, and the CCL2, CCR2 protein expression in the high dose phloretin+GW0742 group were higher than those in the control group (P<0.05), the apoptosis rate of cells was lower than that in the control group (P<0.05). Conclusion: Phloretin may inhibit the malignant progression of lung cancer cells by regulating the CCL2-CCR2 signaling axis-mediated immune response.
蒋莎莎, 杨鹏, 荣丽雯, 曹航. 根皮素调节CCL2-CCR2信号轴对肺癌细胞恶性进展的影响[J]. 河北医学, 2024, 30(7): 1057-1061.
JIANG Shasha, YANG Peng, RONG Liwen, et al. Effect of Phloretin on the Malignant Progression of Lung Cancer Cells by Regulating the CCL2-CCR2 Signaling Axis. HeBei Med, 2024, 30(7): 1057-1061.
[1] 韩宁,李秋实,王鑫洋,等.人参皂苷Rg3抑制肺癌细胞增殖和侵袭的作用及机制[J].中国临床药理学杂志,2023,39(20):2942-2945. [2] 屈贵东,施云飞.肿瘤肺泡腔内播散与肺腺癌的临床病理特征及对肺癌外科治疗和预后影响的研究进展[J].中国肺癌杂志,2019,22(6):363-368. [3] Alsharairi NA.Scutellaria baicalensis and their natural flavone compounds as potential medicinal drugs for the treatment of nicotine-induced non-small-cell lung cancer and asthma[J].Int Environ Res Public Health,2021,18(10):5243-5260. [4] Tuli HS,Rath P,Chauhan A,et al.Phloretin,as a potent anticancer compound:from chemistry to cellular interactions[J].Molecules,2022,27(24):8819-8833. [5] 古双亮,梁旭阳,张瑞,等.根皮素对结肠癌细胞增殖、凋亡及Wnt/β-catenin信号通路的影响[J].胃肠病学和肝病学杂志,2023,32(7):760-764. [6] Hao Q,Vadgama JV,Wang P.CCL2/CCR2 signaling in cancer pathogenesis[J].Cell Commun Signal,2020,18(1):82-94. [7] 胡义阳,余鹏程.根皮素调控NF-κB对MRL/lpr狼疮性肾炎小鼠的保护作用[J].中国免疫学杂志,2019,35(6):722-725+734. [8] 杨羽,黎官印,陈颖,等.雷公藤甲素通过抑制CCL2-CCR2信号通路调节黑色素瘤细胞的增殖、凋亡和免疫逃避[J].中国煤炭工业医学杂志,2023,26(5):449-455. [9] 王志强,周斌锋,彭兵锋,等.姜黄素介导过氧化氢对肺癌细胞A549氧化应激及PI3K/PKC通路的影响[J].中国老年学杂志,2023,43(20):5038-5042. [10] Entezari M,Ghanbarirad M,Taheriazam A,et al.Long non-coding RNAs and exosomal LncRNAs:potential functions in lung cancer progression,drug resistance and tumor microenvironment remodeling[J].Biomed Pharmacother,2022,150(2):112963-112982. [11] Mariadoss AVA,Vinayagam R,Senthilkumar V,et al.Phloretin loaded chitosan nanoparticles augments the pH-dependent mitochondrial-mediated intrinsic apoptosis in human oral cancer cells[J].Int Biol Macromol,2019,130(1):997-1008. [12] Kim JL,Lee DH,Pan CH,et al.Role of phloretin as a sensitizer to TRAIL-induced apoptosis in colon cancer[J].Oncol Lett,2022,24(3):321-333. [13] Xu M,Wang Y,Xia R,et al.Role of the CCL2-CCR2 signalling axis in cancer:mechanisms and therapeutic targeting[J].Cell Prolif,2021,54(10):13115. [14] 徐博雅,杨子桧,王珺,等.CCL2和CCR2在唾液腺腺样囊性癌中的表达及意义[J].中国口腔颌面外科杂志,2019,17(4):311-315. [15] 王静,袁兆林,李伟.毛兰素通过CCL2-CCR2信号轴介导的免疫逃避抑制食管癌细胞的恶性进展[J].河北医学,2023,29(10):1585-1593.