Rahmani-Kukia Nasim, Keshavarzi Fatemeh, Salehi Mohammad Saied, Bozorg-Ghalati Farzaneh, Mojtahedi Zahra, Zamani Mozhdeh, Azarpira Negar, Mokarram Pooneh
Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases. Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mol Biol Res Commun. 2025;14(2):167-175. doi: 10.22099/mbrc.2024.49755.1948.
Human Epidermal Neural Crest Stem Cells (hEPI-NCSCs), as a transient population of multipotent migratory stem cells can differentiate into multiple types of neural and non-neural cells and tissues in the body. Here, we tried to determine the role of chemo agents in mediating the stress induced pathways like autophagy and unfolded protein responses (UPR), as well as the migratory potential of NCSCs. hEPI-NCSCs were treated with chemo agents including Dithiothreitol [(DTT) 10µM)], Salinomycin (9mM), Ebselen (10mM), 5-Fluorouracil [(5-FU) 8µM] and Cisplatin (6mM) for 72 hours. The reverse transcription-quantitative polymerase chain reaction (RT- qPCR) and scratch wound healing assays were used to assess the effect of chemo agents on NCSCs function. After treatment with DTT, hEPI-NCSCs upregulated the expression of genes related to autophagy and UPR pathways including , and . These genes were also overexpressed when NCSCs were treated with Salinomycin. Reverse results were verified by 5-FU, Ebselen and Cisplatin treatment. Salinomycin and Cisplatin upregulated the expression of , which down regulated with DTT, 5-FU and Ebselen. Inhibition in migratory capacity of NCSCs was detected following treatment by Salinomycin, 5-FU, Ebselen and Cisplatin. DTT and 5-FU promoted the expression of , while Salinomycin, Cisplatin and Ebselen treatment reduced its expression. During exposition to DTT, the autophagy pathway was activated, implying that autophagy functions as a survival mechanism for deactivating the inhibitory effects of DTT on the migratory capacity of NCSCs. Chemotherapeutic agents like 5-FU and cisplatin exert cytotoxic effects on NCSCs by suppressing autophagy, UPR pathways, and the migratory potential of NCSCs.
人表皮神经嵴干细胞（hEPI - NCSCs）作为多能迁移干细胞的一个短暂群体，可分化为体内多种类型的神经和非神经细胞及组织。在此，我们试图确定化疗药物在介导自噬和未折叠蛋白反应（UPR）等应激诱导途径以及神经嵴干细胞迁移潜能方面的作用。hEPI - NCSCs用包括二硫苏糖醇[（DTT）10µM]、沙利霉素（9mM）、依布硒啉（10mM）、5 - 氟尿嘧啶[（5 - FU）8µM]和顺铂（6mM）在内的化疗药物处理72小时。采用逆转录定量聚合酶链反应（RT - qPCR）和划痕伤口愈合试验来评估化疗药物对神经嵴干细胞功能的影响。用DTT处理后，hEPI - NCSCs上调了与自噬和UPR途径相关基因的表达，包括 、 和 。当神经嵴干细胞用沙利霉素处理时，这些基因也过表达。5 - FU、依布硒啉和顺铂处理验证了相反的结果。沙利霉素和顺铂上调了 的表达，而DTT、5 - FU和依布硒啉处理则使其下调。用沙利霉素、5 - FU、依布硒啉和顺铂处理后检测到神经嵴干细胞迁移能力受到抑制。DTT和5 - FU促进了 的表达，而沙利霉素、顺铂和依布硒啉处理则降低了其表达。在暴露于DTT期间，自噬途径被激活，这意味着自噬作为一种生存机制，可消除DTT对神经嵴干细胞迁移能力的抑制作用。5 - FU和顺铂等化疗药物通过抑制自噬、UPR途径以及神经嵴干细胞的迁移潜能，对神经嵴干细胞发挥细胞毒性作用。
