Chiou Pey-Tsyr, Ohms Stephen, Board Philip G, Dahlstrom Jane E, Rangasamy Danny, Casarotto Marco G
The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2600, Australia.
Anatomical Pathology, ACT Pathology, Canberra Hospital, Canberra, ACT 2600, Australia.
Cancers (Basel). 2021 Dec 11;13(24):6232. doi: 10.3390/cancers13246232.
Although many breast cancer therapies show initial success in the treatment of the primary tumour, they often fail to eliminate a sub-population of cells known as cancer stem cells (CSCs). These cells are recognised for their self-renewal properties and for their capacity for differentiation often leading to chemo/radio-resistance. The antiviral drug Efavirenz has been shown to be effective in eliminating triple-negative breast cancer cells, and here we examine its effect on breast CSCs. The effects of Efavirenz on CSCs for several breast cancer cell lines were investigated by examining cellular changes upon drug treatment, including CSC numbers, morphology, RNA/microRNA expression and levels of epithelial/mesenchymal CSC subtypes. Efavirenz treatment resulted in a decrease in the size and number of tumorspheres and a reduction in epithelial-type CSC levels, but an increase in mesenchymal-type CSCs. Efavirenz caused upregulation of several CSC-related genes as well as , a CSC marker and , a CSC suppressor gene. We conclude that Efavirenz alters the phenotype and expression of key genes in breast CSCs, which has important potential therapeutic implications.
尽管许多乳腺癌治疗方法在原发性肿瘤的治疗中显示出初步成功,但它们往往无法消除一种被称为癌症干细胞(CSCs)的细胞亚群。这些细胞因其自我更新特性以及分化能力而被识别,这常常导致化疗/放疗耐药性。抗病毒药物依非韦伦已被证明在消除三阴性乳腺癌细胞方面有效,在此我们研究其对乳腺CSCs的影响。通过检查药物处理后的细胞变化,包括CSC数量、形态、RNA/微小RNA表达以及上皮/间充质CSC亚型水平,研究了依非韦伦对几种乳腺癌细胞系CSCs的影响。依非韦伦处理导致肿瘤球的大小和数量减少,上皮型CSC水平降低,但间充质型CSCs增加。依非韦伦导致几个与CSC相关的基因以及一种CSC标志物和一种CSC抑制基因上调。我们得出结论,依非韦伦改变了乳腺CSCs的表型和关键基因的表达,这具有重要的潜在治疗意义。