不同浓度阿达帕林诱导SH-SY5Y细胞的分化及凋亡

刘娜娜; 张俊娇; 张樊; 吴聪英; 姜玉武

doi:10.7499/j.issn.1008-8830.2310100

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中国当代儿科杂志 ›› 2024, Vol. 26 ›› Issue (3) : 282-288. DOI: 10.7499/j.issn.1008-8830.2310100

论著·实验研究

不同浓度阿达帕林诱导SH-SY5Y细胞的分化及凋亡

刘娜娜^1,2, 张俊娇^1,2, 张樊^1,2, 吴聪英³, 姜玉武^1,2

作者信息 +

Different concentrations of adapalene induce differentiation and apoptosis of SH-SY5Y cells

LIU Na-Na^1,2, ZHANG Jun-Jiao^1,2, ZHANG Fan^1,2, WU Cong-Ying³, JIANG Yu-Wu^1,2

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文章历史 +

摘要

目的探讨不同浓度阿达帕林对人神经母细胞瘤细胞系SH-SY5Y细胞形态学及功能的影响，以及诱导细胞分化及凋亡的作用。方法将SH-SY5Y细胞分为对照组、低浓度（0.1 μM和1 μM）阿达帕林组、高浓度（10 μM）阿达帕林组。采用延时显微拍摄技术观察SH-SY5Y细胞形态学变化，采用免疫荧光染色法检测神经元特异性标志物β-微管蛋白Ⅲ和成熟神经元标志物神经丝重链多肽表达，采用多电极阵列记录SH-SY5Y细胞的电生理特征，细胞凋亡检测试剂盒检测细胞凋亡情况。结果低浓度阿达帕林促进SH-SY5Y细胞突起形成，突起之间相互连接形成网络；低浓度阿达帕林处理SH-SY5Y细胞可见自发性放电活动。与对照组比较，1 μM阿达帕林组SH-SY5Y细胞β-微管蛋白Ⅲ和神经丝重链多肽表达升高，高浓度阿达帕林组细胞凋亡水平升高（P<0.05）。结论低浓度阿达帕林可诱导SH-SY5Y细胞分化为成熟的功能性神经元，高浓度阿达帕林可诱导SH-SY5Y细胞凋亡。

Abstract

Objective To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing cell differentiation and apoptosis. Methods SH-SY5Y cells were divided into control group, low concentration (0.1 μM and 1 μM) adapalene groups, and high concentration (10 μM) adapalene group. Time-lapse microscopy was used to observe the morphological changes of SH-SY5Y cells. Immunofluorescence staining was performed to detect the expression of neuronal specific marker βIII-tubulin and mature neuronal marker neurofilament heavy polypeptide (NFH). Multi-electrode array was used to record the electrophysiological features of SH-SY5Y cells. Cell apoptosis was evaluated using a cell apoptosis detection kit. Results Low concentrations of adapalene promoted the formation of neurite outgrowth in SH-SY5Y cells, with the neurites interconnected to form a network. Spontaneous discharge activity was observed in SH-SY5Y cells treated with low concentrations of adapalene. Compared to the control group, the expression of βIII-tubulin and NFH increased in the 1 μM adapalene group, while the level of cell apoptosis increased in the high concentration adapalene group (P<0.05). Conclusions Low concentrations of adapalene can induce differentiation of SH-SY5Y cells into mature functional neurons, while high concentrations of adapalene can induce apoptosis in SH-SY5Y cells.

导出引用

刘娜娜, 张俊娇, 张樊, 吴聪英, 姜玉武. 不同浓度阿达帕林诱导SH-SY5Y细胞的分化及凋亡[J]. 中国当代儿科杂志. 2024, 26(3): 282-288 https://doi.org/10.7499/j.issn.1008-8830.2310100

LIU Na-Na, ZHANG Jun-Jiao, ZHANG Fan, WU Cong-Ying, JIANG Yu-Wu. Different concentrations of adapalene induce differentiation and apoptosis of SH-SY5Y cells[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(3): 282-288 https://doi.org/10.7499/j.issn.1008-8830.2310100

参考文献

1 Zafar A, Wang W, Liu G, et al. Molecular targeting therapies for neuroblastoma: progress and challenges[J]. Med Res Rev, 2021, 41(2): 961-1021. PMID: 33155698. PMCID: PMC7906923. DOI: 10.1002/med.21750.
2 Louis CU, Shohet JM. Neuroblastoma: molecular pathogenesis and therapy[J]. Annu Rev Med, 2015, 66: 49-63. PMID: 25386934. PMCID: PMC4418018. DOI: 10.1146/annurev-med-011514-023121.
3 Qin H, Yang S, Cai S, et al. Clinical characteristics and risk factors of 47 cases with ruptured neuroblastoma in children[J]. BMC Cancer, 2020, 20(1): 243. PMID: 32293329. PMCID: PMC7092550. DOI: 10.1186/s12885-020-06720-9.
4 Fjodorova M, Noakes Z, Li M. A role for TGFβ signalling in medium spiny neuron differentiation of human pluripotent stem cells[J]. Neuronal Signal, 2020, 4(2): NS20200004. PMID: 32714602. PMCID: PMC7373249. DOI: 10.1042/NS20200004.
5 Lin YL, Lin YW, Nhieu J, et al. Sonic hedgehog-Gli1 signaling and cellular retinoic acid binding protein 1 gene regulation in motor neuron differentiation and diseases[J]. Int J Mol Sci, 2020, 21(11): 4125. PMID: 32527063. PMCID: PMC7312406. DOI: 10.3390/ijms21114125.
6 De Gregorio R, Pulcrano S, De Sanctis C, et al. miR-34b/c regulates Wnt1 and enhances mesencephalic dopaminergic neuron differentiation[J]. Stem Cell Reports, 2018, 10(4): 1237-1250. PMID: 29526736. PMCID: PMC5998209. DOI: 10.1016/j.stemcr.2018.02.006.
7 Ben-Shushan E, Feldman E, Reubinoff BE. Notch signaling regulates motor neuron differentiation of human embryonic stem cells[J]. Stem Cells, 2015, 33(2): 403-415. PMID: 25335858. DOI: 10.1002/stem.1873.
8 Girardi CS, Rostirolla DC, Lini FJM, et al. Nuclear RXRα and RXRβ receptors exert distinct and opposite effects on RA-mediated neuroblastoma differentiation[J]. Biochim Biophys Acta Mol Cell Res, 2019, 1866(3): 317-328. PMID: 30529222. DOI: 10.1016/j.bbamcr.2018.11.014.
9 Arooj A, Rehman AU, Iqbal M, et al. Development of adapalene loaded liposome based gel for acne[J]. Gels, 2023, 9(2): 135. PMID: 36826305. PMCID: PMC9956198. DOI: 10.3390/gels9020135.
10 Jain AK, Jain A, Garg NK, et al. Adapalene loaded solid lipid nanoparticles gel: an effective approach for acne treatment[J]. Colloids Surf B Biointerfaces, 2014, 121: 222-229. PMID: 25016424. DOI: 10.1016/j.colsurfb.2014.05.041.
11 Li H, Wang C, Li L, et al. Adapalene suppressed the proliferation of melanoma cells by S-phase arrest and subsequent apoptosis via induction of DNA damage[J]. Eur J Pharmacol, 2019, 851: 174-185. PMID: 30836068. DOI: 10.1016/j.ejphar.2019.03.004.
12 Wang C, Li H, Ma P, et al. The third-generation retinoid adapalene triggered DNA damage to induce S-phase arrest in HaCat cells[J]. Fundam Clin Pharmacol, 2020, 34(3): 380-388. PMID: 31808972. DOI: 10.1111/fcp.12527.
13 Mehraj U, Mir IA, Hussain MU, et al. Adapalene and doxorubicin synergistically promote apoptosis of TNBC cells by hyperactivation of the ERK1/2 pathway through ROS induction[J]. Front Oncol, 2022, 12: 938052. PMID: 35875119. PMCID: PMC9298514. DOI: 10.3389/fonc.2022.938052.
14 Mehraj U, Wani NA, Hamid A, et al. Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941[J]. Front Pharmacol, 2022, 13: 958443. PMID: 36003501. PMCID: PMC9393306. DOI: 10.3389/fphar.2022.958443.
15 Ocker M, Herold C, Ganslmayer M, et al. The synthetic retinoid adapalene inhibits proliferation and induces apoptosis in colorectal cancer cells in vitro[J]. Int J Cancer, 2003, 107(3): 453-459. PMID: 14506747. DOI: 10.1002/ijc.11410.
16 Xicoy H, Wieringa B, Martens GJ. The SH-SY5Y cell line in Parkinson's disease research: a systematic review[J]. Mol Neurodegener, 2017, 12(1): 10. PMID: 28118852. PMCID: PMC5259880. DOI: 10.1186/s13024-017-0149-0.
17 Ioghen OC, Ceafalan LC, Popescu BO. SH-SY5Y cell line in vitro models for parkinson disease research-old practice for new trends[J]. J Integr Neurosci, 2023, 22(1): 20. PMID: 36722247. DOI: 10.31083/j.jin2201020.
18 Xie HR, Hu LS, Li GY. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease[J]. Chin Med J (Engl), 2010, 123(8): 1086-1092. PMID: 20497720.
19 Cai A, Lin Z, Liu N, et al. Neuroblastoma SH-SY5Y cell differentiation to mature neuron by AM580 treatment[J]. Neurochem Res, 2022, 47(12): 3723-3732. PMID: 36066699. PMCID: PMC9718880. DOI: 10.1007/s11064-022-03730-w.
20 Martin ER, Gandawijaya J, Oguro-Ando A. A novel method for generating glutamatergic SH-SY5Y neuron-like cells utilizing B-27 supplement[J]. Front Pharmacol, 2022, 13: 943627. PMID: 36339621. PMCID: PMC9630362. DOI: 10.3389/fphar.2022.943627.
21 Zhang T, Gygi SP, Paulo JA. Temporal proteomic profiling of SH-SY5Y differentiation with retinoic acid using FAIMS and real-time searching[J]. J Proteome Res, 2021, 20(1): 704-714. PMID: 33054241. PMCID: PMC8210949. DOI: 10.1021/acs.jproteome.0c00614.