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褪黑素调节癌症迁移和干性并增强顺铂的抗肿瘤作用。

Melatonin regulates cancer migration and stemness and enhances the anti-tumour effect of cisplatin.

机构信息

College of Life and Health Sciences, Northeastern University, Shenyang, China.

Liaoning Center for Animal Disease Control and Prevention, Liaoning Agricultural Development Service Center, Shenyang, China.

出版信息

J Cell Mol Med. 2023 Aug;27(15):2215-2227. doi: 10.1111/jcmm.17809. Epub 2023 Jun 12.

DOI:10.1111/jcmm.17809
PMID:37307404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10399526/
Abstract

Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133 cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133 cells compared to CD133 cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.

摘要

褪黑素是一种由松果体分泌的亲脂性激素，对多种类型的癌症具有生长抑制作用。然而，为了提高其癌症治疗的潜力，需要对其相应的作用机制进行解析，并优化治疗策略。在本研究中，褪黑素抑制了胃癌细胞的迁移和软琼脂集落形成。采用磁激活细胞分选法分离 CD133 肿瘤干细胞。基因表达分析显示，与 CD133 细胞相比，褪黑素降低了 CD133 细胞中 LC3-II 表达的上调。褪黑素处理的细胞中，一些长链非编码 RNA 和经典 Wnt 信号通路的许多成分发生了改变。此外，敲低长链非编码 RNA H19 增强了褪黑素处理诱导的促凋亡基因 Bax 和 Bak 的表达。研究了褪黑素与顺铂联合治疗以提高褪黑素作为抗癌治疗的适用性。联合治疗增加了细胞凋亡率，并诱导了 G0/G1 细胞周期停滞。褪黑素可通过调节多种信号通路来调节胃癌细胞的迁移和干性。褪黑素与顺铂联合治疗有可能提高两者的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/340f/10399526/a9197a1fdfa4/JCMM-27-2215-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/340f/10399526/7dac93561de0/JCMM-27-2215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/340f/10399526/3e2d7c1a1192/JCMM-27-2215-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/340f/10399526/c2f1738c97cb/JCMM-27-2215-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/340f/10399526/0edceeaa50a8/JCMM-27-2215-g006.jpg
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