Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells.
Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells.
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DOI：
10.1038/s41416-021-01499-3
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发表时间：
2021-09
影响因子：
8.8
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Zou Z;Zheng W;Fan H;Deng G;Lu SH;Jiang W;Yu X
肿瘤干细胞（Cancer stem cells, CSCs）与食管鳞状细胞癌（ESCC）患者的预后、复发和治疗抵抗有关。尽管越来越多的证据表明阿司匹林（乙酰水杨酸，ASA）可以降低ESCC的发病率并改善预后，但其机制仍有待充分了解。我们在人ESCC细胞系和n -亚硝基甲基苄胺诱导的大鼠ESCC癌变模型中研究了ASA在化疗/化学预防中的作用。在体外和体内观察ASA/顺铂联合治疗对ESCC细胞株的影响。我们利用富含推测CSCs的球形细胞（pCSCs）来研究ASA对CSCs的影响。采用转座酶可及染色质高通量测序（ATAC-seq）测定ASA对ESCC细胞染色质可及性的影响。ASA抑制人ESCC细胞的CSC特性并增强顺铂治疗。ATAC-seq表明，ASA处理通过改变组蛋白乙酰化水平，导致ESCC细胞，特别是pcsc中染色质发生显著的表观遗传改变。在ESCC的CSCs中，表观遗传改变激活了Bim的表达，促进了细胞的死亡。此外，ASA可阻止nmbza诱导的ESCC在大鼠模型中的癌变。ASA可能成为ESCC治疗的潜在化疗辅助药物和化学预防药物。
Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.
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影响因子：
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