Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland.
Department of Neurosurgery, Medical University of Bialystok, M. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.
Int J Mol Sci. 2020 Jul 17;21(14):5039. doi: 10.3390/ijms21145039.
Multidrug resistance (MDR) is an emerging problem in the treatment of cancer. Therefore, there is a necessity for novel strategies that would sensitize tumor cells to the administered chemotherapeutics. One of the innovative approaches in fighting drug-resistant tumors is the treatment of cancer with microRNA (miRNA), or the use of cubosomes (lipid nanoparticles) loaded with drugs. Here, we present a study on a novel approach, which combines both tools.
Cubosomes loaded with miR-7-5p and chemotherapeutics were developed. The effects of drug- and miRNA-loaded vehicles on glioma- (A172, T98G), papillary thyroid- (TPC-1) and cervical carcinoma-derived (HeLa) cells were analyzed using molecular biology techniques, including quantitative real-time PCR, MTS-based cell proliferation test, flow cytometry and spheroids formation assay.
The obtained data indicate that miR-7-5p increases the sensitivity of the tested cells to the drug, and that nanoparticles loaded with both miRNA and the drug produce a greater anti-tumor effect in comparison to the free drug treatment. It was found that an increased level of apoptosis in the drug/miRNA co-treated cells is accompanied by an alternation in the expression of the genes encoding for key MDR proteins of the ABC family.
Overall, co-administration of miR-7-5p with a chemotherapeutic can be considered a promising strategy, leading to reduced MDR and the induction of apoptosis in cancer cells.
多药耐药（MDR）是癌症治疗中出现的一个新问题。因此，有必要寻找新的策略，使肿瘤细胞对给予的化疗药物敏感。对抗耐药肿瘤的创新方法之一是用 microRNA（miRNA）治疗癌症，或使用载药的 cubosomes（脂质纳米粒）。在这里，我们提出了一种新的方法，该方法结合了这两种工具。
制备负载 miR-7-5p 和化疗药物的 cubosomes。使用分子生物学技术，包括定量实时 PCR、MTS 基于细胞增殖试验、流式细胞术和球体形成测定，分析载药和 miRNA 载体对神经胶质瘤（A172、T98G）、甲状腺乳头状癌（TPC-1）和宫颈癌衍生（HeLa）细胞的影响。
获得的数据表明，miR-7-5p 增加了测试细胞对药物的敏感性，并且负载 miRNA 和药物的纳米粒与游离药物治疗相比产生了更大的抗肿瘤作用。研究发现，药物/miRNA 共同处理细胞中凋亡的增加伴随着 ABC 家族中关键 MDR 蛋白编码基因表达的改变。
总之，miR-7-5p 与化疗药物联合给药可以被认为是一种有前途的策略，可降低 MDR 并诱导癌细胞凋亡。
