فهرست مطالب mahshid samie ghahfarokhi

Herbal compounds with cytotoxicity have been of great interest in recent years to improve cancer treatment methods. Fisetin is an anti-cancer herbal compound with low solubility in aqueous systems. Metformin is another compound with anti-cancer effects. In this study, the combined effect of fisetin and metformin was investigated using mesoporous silica nanoparticles (MSNs) in breast cancer cell lines. 

After the synthesis of nanoparticles, they were characterized using XRD, TEM, SEM. The DLS test showed a size of 143.4 nm with zeta-potential -39.1 mV. Fisetin and metformin were loaded into nanoparticles and loading was confirmed by FTIR. The toxicity of different concentrations of free drug (metformin, fisetin, fisetin-metformin) and Nanoformulations (metformin, fisetin and nano-fisetin-metformin) was investigated on two breast cancer lines MCF7 and MDA-MB-231. 

Fisetin-metformin co-loaded in MSNs showed the highest cytotoxicity among all formulations in both cell lines. The inhibition of colony formation and migration rate was effectively observed in the co-treatment of cells with fisetin and metformin loaded in nanoparticles compared to single treatments. The expression of tumor suppressor miR-200b-3p and miR-34a-5p showed that fisetin increased the expression of these tumor suppressors compared to the control. 

The anti-cancer effect of fisetin-metformin in combination increased the expression of tumor suppressors due to the regulation of a wide range of gene network involving in cancer progress. The obtained results highlight the use of MSN as an effective drug delivery system for simultaneous delivery of herbal cytotoxic compounds in cancer.

miRNAs are small non-coding RNAs; regulate gene expression using RNA degradation or translation repression. Dysregulation of miRNAs is involved in the initiation and progression of many cancers. We aimed to determine the relationship between miR-5571-5p expression and clinical factors and regulatory mechanisms in breast cancer.

Histopathologic sections approximately with 25 microns thick from FFPE tissues were achievement of Al-Zahra Hospital (Isfahan, Iran) in 2020-2021 years by Pathologist. miR-5571-5p expression, determined using real-time PCR. For miRNA target genes prediction, integrated miRNA target prediction tools, were used. Gene ontology and KEGG pathway analysis were accomplished to identify the biological function. A PPI network was constructed to display key target genes. For hub genes validation, GEPIA databases were used.

miR-5571-5p was upregulated in breast tumor tissues, and its increase was significantly related to a poor prognosis in breast cancer (P<0.0001). At first, 324 target genes were predicted, and then 110 genes with a decrease in expression were selected. GO analysis showed that genes were mainly enriched in the regulation of the ERBB2 and EGFR signaling pathway. KEGG pathway analysis suggested that downregulated genes were enriched in glioma, the ErbB signaling pathway, and breast cancer. Finally, the ten hub genes (EGF, PIK3R1, SOS1, PTEN, SHC1, CBLB, LIFR, LEP, PDE1C, and NT5C2) were detected from the PPI network.

miR-5571-5p up-regulation is associated with breast cancer progression and worse survival. The current study identified ten genes associated with breast cancer, which might help to provide candidate targets for the treatment.