Department of Respiratory and Critical Care Medicine, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfuqian Street, Erqi District, Zhengzhou, 450052, China.
School of Textiles, Zhongyuan University of Technology, No. 41 Zhongyuan Road (M), Zhengzhou, 450007, China.
Biochem Biophys Res Commun. 2019 Apr 30;512(2):218-223. doi: 10.1016/j.bbrc.2019.03.060. Epub 2019 Mar 15.
Recently, the incidence of lung cancer is generally rising along with air pollution and smoking, and non-small cell lung cancer (NSCLC) accounts for nearly 85% among all lung cancer diagnoses. With the development of chemotherapy, the drug resistance rate of common platinum-based chemotherapeutic drugs (like cisplatin) is gradually increased, which seriously affects the chemotherapy efficiency and survival rate of patients. In this study, polyethylenimine caged platinum nanoclusters (PEI-caged Pt NCs) were proposed as a new chemotherapeutic agent to apply in the treatment of NSCLC, choosing the classical cisplatin-resistant A549/DDP cells and normal A549 cells as targets. It was found that our Pt NCs-based chemotherapeutic drugs showed its preferable therapeutic effect in cisplatin-resistant NSCLC through the results of confocal microscopic images, cell counting kit-8 test, cell apoptosis assay and western blot. Most importantly, in the cisplatin-resistance A549/DDP cells, this kind of agents could enter the nucleus obviously, and emerged a superior inhibitory and apoptotic effects than A549 via activating p53 protein and the related signaling pathways. Comparing with the traditional chemotherapy drugs, these Pt NCs-based chemotherapeutic agents exhibit great potential and advantages in the treatment and diagnosis of NSCLC regardless of the therapeutic effect or toxic side effects, especially the drug resistance.
近年来,随着空气污染和吸烟的增加,肺癌的发病率普遍呈上升趋势,而非小细胞肺癌(NSCLC)约占所有肺癌诊断的 85%。随着化疗的发展,常见的铂类化疗药物(如顺铂)的耐药率逐渐升高,严重影响了患者的化疗效果和生存率。在这项研究中,我们提出了聚乙烯亚胺笼状铂纳米团簇(PEI-caged Pt NCs)作为一种新的化疗药物,应用于 NSCLC 的治疗,选择经典的顺铂耐药 A549/DDP 细胞和正常 A549 细胞作为靶细胞。通过共聚焦显微镜图像、细胞计数试剂盒-8 试验、细胞凋亡试验和 Western blot 结果发现,我们的基于 Pt NCs 的化疗药物在顺铂耐药 NSCLC 中表现出更好的治疗效果。最重要的是,在顺铂耐药 A549/DDP 细胞中,这种药物可以明显进入细胞核,并通过激活 p53 蛋白和相关信号通路,表现出比 A549 更优的抑制和凋亡作用。与传统的化疗药物相比,这些基于 Pt NCs 的化疗药物在 NSCLC 的治疗和诊断中具有很大的潜力和优势,无论在治疗效果还是毒副作用方面,尤其是耐药性方面。