Rawangkan Anchalee, Wongsirisin Pattama, Pook-In Grissana, Siriphap Achiraya, Yosboonruang Atchariya, Kiddee Anong, Chuerduangphui Jureeporn, Reukngam Nanthawan, Duangjai Acharaporn, Saokaew Surasak, Praphasawat Ratsada
Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
UNIt of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand.
Antibiotics (Basel). 2022 Dec 19;11(12):1845. doi: 10.3390/antibiotics11121845.
Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1-1 µM of dinactin suppresses cell growth through induction of the G/G phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., , , , and ) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs.
肺癌，尤其是非小细胞肺癌（NSCLC），是最复杂的疾病之一，尽管存在化疗和免疫疗法等有效治疗方法。由于癌症干细胞（CSCs）导致化疗和放疗耐药、转移及癌症复发，因此寻找针对癌症干细胞的新治疗靶点至关重要。迪那菌素是微生物产生的一种天然次生代谢产物。最近，迪那菌素已通过多种机制被揭示为一种有前景的抗肿瘤抗生素。然而，与细胞周期进程调控相关的证据有限，且其对癌症干性的影响尚未阐明。因此，本研究的目的是评估迪那菌素在抗NSCLC增殖方面的新功能，重点关注其对Lu99和A549细胞的细胞周期进程及癌症干性特性的影响。流式细胞术和免疫印迹分析显示，0.1 - 1 μM的迪那菌素通过诱导与细胞周期蛋白A、B和D3以及细胞周期蛋白依赖性激酶2（cdk2）蛋白表达下调相关的G/G期来抑制细胞生长。肿瘤球形成能力用于评估迪那菌素对NSCLC细胞癌症干性潜能的影响。在1 nM的浓度下，迪那菌素减少了肿瘤球的数量和大小。定量逆转录聚合酶链反应（qRT-PCR）分析表明，迪那菌素通过显著降低Lu99细胞中癌症干细胞标志物（即 、 、 和 ）的表达来抑制球形成。因此，迪那菌素可能是一种有前景的针对癌症干细胞的NSCLC治疗策略。 （注：原文中部分CSC标志物未给出具体名称，所以用“ 、 、 和 ”表示）
