Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: Identification of potential candidate genes and pathways by transcriptome analysis.
Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: Identification of potential candidate genes and pathways by transcriptome analysis.
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姜黄素诱导细胞凋亡并抑制肾上腺皮质癌的生长：通过转录组分析鉴定潜在的候选基因和通路
DOI：
10.3892/ol.2021.12737
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发表时间：
2021-06
期刊：
影响因子：
2.9
通讯作者：
Luo Z
中科院分区：
文献类型：
--
作者：
Huang X;Liang C;Yang H;Li X;Deng X;Liang X;Li L;Huang Z;Lu D;Ma Y;Luo Z
肾上腺皮质癌（ACC）是一种恶性程度高、侵袭性强且预后较差的内分泌肿瘤。姜黄素是姜黄的主要成分，据报道其在癌症治疗方面具有良好疗效和生物安全性。然而，姜黄素在肾上腺皮质癌中的作用及机制尚未得到充分研究，因此本研究聚焦于此。在体外实验中，用姜黄素处理肾上腺皮质癌SW - 13和NCI - H295R细胞，通过CCK - 8法和Transwell实验评估细胞活力、迁移及侵袭能力。采用流式细胞术和蛋白质免疫印迹法检测细胞凋亡情况。通过高通量测序和综合生物信息学分析来阐明姜黄素发挥作用的分子过程。在体内实验中，将SW - 13细胞注入裸鼠体内，姜黄素处理2周后观察肿瘤体积和重量。通过电子显微镜观察细胞器变化，并采用逆转录 - 定量聚合酶链反应（RT - qPCR）和蛋白质免疫印迹法分析潜在的候选基因和信号通路。通过慢病毒转染实验验证CHOP靶基因在姜黄素诱导的肾上腺皮质癌细胞凋亡中的作用。结果显示，姜黄素抑制了肾上腺皮质癌细胞的活力、迁移和侵袭能力，并诱导细胞凋亡。转录组测序分析表明，姜黄素处理显著改变了基因表达水平。基因本体论（Gene Ontology）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）通路富集分析显示，丝裂原活化蛋白激酶（MAPK）和内质网（ER）应激通路是与姜黄素诱导肾上腺皮质癌细胞凋亡相关的主要通路。后续体内外实验结果表明，在经姜黄素处理的肾上腺皮质癌细胞中，c - Jun氨基末端激酶（JNK）、p38丝裂原活化蛋白激酶（p38 MAPK）和内质网应激通路被激活，且C / EBP同源蛋白（CHOP）的诱导是姜黄素诱导肾上腺皮质癌细胞凋亡的原因。综上所述，姜黄素通过激活JNK、p38 MAPK和内质网应激通路诱导肾上腺皮质癌细胞凋亡并抑制肿瘤生长。因此，姜黄素可能是一种有潜力的肾上腺皮质癌治疗药物。
Adrenocortical carcinoma (ACC) is an endocrine tumour with high malignancy, high invasiveness and poor prognosis. Curcumin, a major component in turmeric, has been reported to have good efficacy and biological safety in treating cancer. However, the role and mechanism of curcumin in ACC have not yet been fully investigated and were thus the focus of this study. In vitro, ACC SW-13 and NCI-H295R cells were treated with curcumin and their viability, migration and invasion were assessed by CCK-8 and Transwell assays. Apoptosis was detected via flow cytometry and western blotting. High-throughput sequencing and comprehensive bioinformatics analyses were performed to elucidate the molecular processes underlying curcumin activity. In vivo, SW-13 cells were injected into nude mice, and the tumour volumes and weights were observed after 2 weeks of curcumin treatment. Organelle changes were observed by electron microscopy, and potential candidate genes and pathways were analysed by RT-qPCR and western blotting. The role of the CHOP target gene in curcumin-induced ACC cell apoptosis was verified via lentiviral transfection experiments. Curcumin inhibited the viability, migration and invasion, and induced the apoptosis of ACC cells. Transcriptome sequencing analysis showed that curcumin treatment markedly changed the gene expression levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the MAPK and endoplasmic reticulum (ER) stress pathways were the predominant pathways associated with curcumin-induced apoptosis of ACC cells. Subsequent in vivo and in vitro results demonstrated that the JNK, p38 MAPK and ER stress pathways were activated in curcumin-treated ACC cells, and that C/EBP homologous protein induction was responsible for curcumin-induced apoptosis of ACC cells. In summary, curcumin induced ACC cell apoptosis and inhibited tumour growth by activating the JNK, p38 MAPK and ER stress pathways. Thus, curcumin may be a potential therapeutic drug for ACC.
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影响因子：
11.2
作者：
Chadalapaka G;Jutooru I;Chintharlapalli S;Papineni S;Smith R 3rd;Li X;Safe S
通讯作者：
Safe S
影响因子：
3.7
作者：
Mathur A;Abd Elmageed ZY;Liu X;Kostochka ML;Zhang H;Abdel-Mageed AB;Mondal D
通讯作者：
Mondal D
影响因子：
2.4
作者：
Chen, Ling;Zhan, Cheng-Zhi;Yao, Rui
通讯作者：
Yao, Rui
DOI：
10.1007/978-1-4939-7477-1_27
发表时间：
2018-01-01
期刊：
CHAPERONES
影响因子：
--
作者：
Boudesco, Christophe;Cause, Sebastien;Garrido, Carmen
通讯作者：
Garrido, Carmen
影响因子：
7.2
作者：
Choi, Ji Hyun;Jeong, Yeon Ju;Kang, Insug
通讯作者：
Kang, Insug