Xiao Dayong, Hu Xinlei, Zhang Juan
Department of Thoracic and Cardiovascular Surgery, People's Hospital of Wanning City, Wanning, Hainan, China.
Department of Endocrinology, Handan First Hospital, Handan, Hebei, China.
J Drug Target. 2022 Jun;30(5):534-543. doi: 10.1080/1061186X.2021.2016773. Epub 2022 Mar 7.
Multi-drug resistance (MDR) is the major hindrance towards the successful treatment of malignant lung cancer. The aim of this study was to develop a novel nanoparticle co-loaded with docetaxel (DTX) and si-colon cancer-associated transcript-2 (siCCAT2) (NP-DTX/siCCAT2) for overcoming the DTX-resistant non-small cell lung cancer (NSCLC). The NP-DTX/siCCAT2, developed by DTX-conjugated poly (D,L-lactic-co-glycolic acid) (PLGA) copolymers, has an average size of 87.26 nm. Further modification of Transferrin (Tf) peptides on the surface of NP-DTX/siCCAT2 did not significantly change the particle size with an average diameter of 96.81 nm. The present study demonstrated that TfNP-DTX/siCCAT2 has excellent tumour targeting ability and resulted in an enhanced anti-tumour effect both and experiments. Not unexpectedly, a more excellent anti-tumour effect of NP-DTX/siCCAT2 was obtained than the NP-DTX because the silencing of CCAT2 levels in lung cancer cells resulted in down-regulated expressions of P-glycoprotein (P-gp) and multidrug-resistance-associated proteins 1 (MRP1). Further investigation revealed that inhibition of CCAT2 expression dramatically increased the activity of miR-204-3p and thereby signally suppressed the IGFBP2/AKT/Bcl2 pathway.
多药耐药性（MDR）是恶性肺癌成功治疗的主要障碍。本研究的目的是开发一种新型纳米颗粒，其同时负载多西他赛（DTX）和结肠癌相关转录本2小干扰RNA（siCCAT2）（NP-DTX/siCCAT2），以克服对DTX耐药的非小细胞肺癌（NSCLC）。由DTX共轭聚（D，L-乳酸-共-乙醇酸）（PLGA）共聚物开发的NP-DTX/siCCAT2，平均粒径为87.26nm。在NP-DTX/siCCAT2表面进一步修饰转铁蛋白（Tf）肽，平均直径为96.81nm，粒径没有显著变化。本研究表明，TfNP-DTX/siCCAT2具有优异的肿瘤靶向能力，在体内和体外实验中均产生了增强的抗肿瘤效果。不出所料，NP-DTX/siCCAT2比NP-DTX具有更优异的抗肿瘤效果，因为肺癌细胞中CCAT2水平的沉默导致P-糖蛋白（P-gp）和多药耐药相关蛋白1（MRP1）的表达下调。进一步研究发现，抑制CCAT2表达显著增加了miR-204-3p的活性，从而显著抑制了IGFBP2/AKT/Bcl2通路。
