Combinatory Treatment with miR-7-5p and Drug-Loaded Cubosomes Effectively Impairs Cancer Cells

被引:43
作者
Gajda, Ewa [1 ]
Godlewska, Marlena [1 ]
Mariak, Zenon [2 ]
Nazaruk, Ewa [3 ]
Gawel, Damian [1 ,4 ]
机构
[1] Ctr Postgrad Med Educ, Dept Biochem & Mol Biol, Marymoncka 99-103, PL-01813 Warsaw, Poland
[2] Med Univ Bialystok, Dept Neurosurg, M Sklodowskiej Curie 24A, PL-15276 Bialystok, Poland
[3] Univ Warsaw, Fac Chem, Pasteura 1, PL-02093 Warsaw, Poland
[4] Ctr Postgrad Med Educ, Dept Immunohematol, Marymoncka 99-103, PL-01813 Warsaw, Poland
关键词
miR-7-5p; cubosomes; multidrug resistance; cancer cells; glioblastoma; temozolomide; doxorubicin; MESOPOROUS SILICA NANOPARTICLES; MULTIDRUG-RESISTANCE; CO-DELIVERY; PROLIFERATION; EXPRESSION; APOPTOSIS; TEMOZOLOMIDE; DOXORUBICIN; MICRORNA-7; PROGRESSION;
D O I
10.3390/ijms21145039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
引用
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页码:1 / 19
页数:19
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