Huang Xuemei, Liang Chunfeng, Yang Haiyan, Li Xin, Deng Xiujun, Liang Xinghuan, Li Li, Huang Zhenxing, Lu Decheng, Ma Yan, Luo Zuojie
Department of Endocrinology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530022, P.R. China.
Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Oncol Lett. 2021 Jun;21(6):476. doi: 10.3892/ol.2021.12737. Epub 2021 Apr 15.
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. , 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. , 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 and 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.
肾上腺皮质癌(ACC)是一种恶性程度高、侵袭性强且预后不良的内分泌肿瘤。姜黄素是姜黄中的主要成分,据报道在癌症治疗中具有良好的疗效和生物安全性。然而,姜黄素在ACC中的作用和机制尚未得到充分研究,因此是本研究的重点。将ACC SW-13和NCI-H295R细胞用姜黄素处理,通过CCK-8和Transwell实验评估其活力、迁移和侵袭能力。通过流式细胞术和蛋白质印迹法检测细胞凋亡。进行高通量测序和综合生物信息学分析以阐明姜黄素活性背后的分子过程。将SW-13细胞注射到裸鼠体内,在姜黄素治疗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,并通过RT-qPCR和蛋白质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了CHOP靶基因在姜黄素诱导的ACC细胞凋亡中的作用。姜黄素抑制了ACC细胞的活力、迁移和侵袭,并诱导了其凋亡。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。基因本体论和京都基因与基因组百科全书信号通路富集分析表明,MAPK和内质网(ER)应激信号通路是与姜黄素诱导的ACC细胞凋亡相关的主要信号通路。随后的结果表明,在姜黄素处理的ACC细胞中JNK、p38 MAPK和ER应激信号通路被激活,并且C/EBP同源蛋白的诱导是姜黄素诱导ACC细胞凋亡的原因。总之,姜黄素通过激活JNK、p38 MAPK和ER应激信号通路诱导ACC细胞凋亡并抑制肿瘤生长。因此,姜黄素可能是ACC的一种潜在治疗药物。