Combinatory Treatment with miR-7-5p and Drug-Loaded Cubosomes Effectively Impairs Cancer Cells
Ewa Gajda1, Marlena Godlewska1, Zenon Mariak2
1Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland.
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.
Insights
This study shows that combining microRNA-7-5p (miR-7-5p) with chemotherapy in cubosomes enhances anti-tumor effects and overcomes multidrug resistance (MDR) in cancer cells.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Research
Background:
- Multidrug resistance (MDR) poses a significant challenge in cancer treatment.
- Novel strategies are needed to sensitize drug-resistant tumor cells.
- MicroRNA (miRNA) therapy and drug-loaded cubosomes are innovative approaches.
Purpose of the Study:
- To investigate a novel approach combining miR-7-5p and chemotherapeutics within cubosomes.
- To evaluate the efficacy of this combined therapy against various cancer cell lines.
Main Methods:
- Development of cubosomes co-loaded with miR-7-5p and chemotherapeutics.
- Analysis of cellular response using quantitative real-time PCR, MTS assay, flow cytometry, and spheroids formation assay.
- Testing on glioma, papillary thyroid, and cervical carcinoma cell lines.
Main Results:
- miR-7-5p significantly increased cancer cell sensitivity to chemotherapeutics.
- Co-loaded cubosomes demonstrated a greater anti-tumor effect than free drugs.
- Apoptosis induction was observed, with altered expression of ABC family MDR proteins.
Conclusions:
- Co-administration of miR-7-5p with chemotherapeutics is a promising strategy.
- This approach effectively reduces multidrug resistance.
- The combination therapy induces apoptosis in cancer cells.
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