Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Center for Studies of Psychological Application, South China Normal University, Guangzhou, China.
The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):53-59. doi: 10.1080/21691401.2019.1699808.
Gramicidin is a well-known antibiotic and recently was reported to induced tumour cell death, however, little is understood about the molecular mechanism of gramicidin as a therapeutic agent for solid tumours. Here, we investigated the role of gramicidin in cholangiocarcinoma cells. We found that gramicidin A inhibits cholangiocarcinoma cell growth and induced the necrotic cell death. We used next generation sequencing to analyse gene expression profiles of cholangiocarcinoma cells treated with gramicidin. We identified 265 differentially expressed genes in cholangiocarcinoma cells between PBS treatment and gramicidin treatment. EGR4 was confirmed to be a target of gramicidin-induced cell growth inhibition. Furthermore, we demonstrated that downregulation of EGR4 in cholangiocarcinoma cells leads to restraining tumour cell growth. Of note, EGR4 was expressed at highest levels in cholangiocarcinoma tissues among 17 types of human cancers, and EGR4 expression positively correlated with several growth factors associated with cholangiocarcinoma. Our findings ascertain that EGR4 is a potential target in cholangiocarcinoma and suppressing EGR4 by gramicidin establish an essential mechanism for bile duct carcinoma progression.
短杆菌肽是一种众所周知的抗生素，最近有报道称其可诱导肿瘤细胞死亡，但对于短杆菌肽作为实体瘤治疗药物的分子机制知之甚少。在这里，我们研究了短杆菌肽在胆管癌细胞中的作用。我们发现短杆菌肽 A 抑制胆管癌细胞生长并诱导细胞坏死性死亡。我们使用下一代测序技术分析了用短杆菌肽处理的胆管癌细胞的基因表达谱。我们在 PBS 处理和短杆菌肽处理的胆管癌细胞之间鉴定了 265 个差异表达基因。EGR4 被确认为短杆菌肽诱导的细胞生长抑制的靶标。此外，我们证明下调胆管癌细胞中的 EGR4 可抑制肿瘤细胞生长。值得注意的是，在 17 种人类癌症中，EGR4 在胆管癌组织中表达水平最高，并且 EGR4 的表达与几种与胆管癌相关的生长因子呈正相关。我们的研究结果证实 EGR4 是胆管癌的一个潜在靶点，而短杆菌肽抑制 EGR4 则建立了胆管癌进展的重要机制。
