Ultrasound‑targeted microbubble destruction‑mediated miR‑205 enhances cisplatin cytotoxicity in prostate cancer cells

Abstract

MicroRNAs (miRNAs) are non-coding ~20 nucleotides long sequences that function in the initiation and development of a number of cancers. Ultrasound-targeted microbubble destruction (UTMD) is an effective method for microRNA delivery. The aim of the present study was to investigate the potential roles of UTMD-mediated miRNA (miR)-205 delivery in the development of prostate cancer (PCa). In the present study, miR-205 expression was examined by reverse transcription-quantitative polymerase chain reaction assay. miR-205 mimics were transfected into PC-3 cells using the UTMD method, and the PC-3 cells were also treated with cisplatin. Cell proliferation, apoptosis, migration and invasion abilities were detected using Cell Counting kit-8, flow cytometry, wound healing and Transwell assays, respectively. In addition, the protein expression levels of caspase-9, cleaved-caspase 9, cytochrome c (cytoc), epithelial (E)-cadherin, matrix metalloproteinase-9 (MMP-9), phosphorylated (p)-extracellular signal-regulated kinase (ERK) and ERK were measured by western blot analysis. The results of the present study demonstrated that miR-205 expression was low in human PCa cell lines compared with healthy cells and that UTMD-mediated miR-205 delivery inhibited PCa cell proliferation, migration and invasion, and promoted apoptosis modulated by cisplatin compared with UTMD-mediated miR-negative control group and miR-205-treated group. Furthermore, it was demonstrated that UTMD-mediated miR-205 transfection increased the expression of caspase-9, cleaved-caspase 9, cytochrome c and E-cadherin, and decreased the expression of MMP-9 and p-ERK. Therefore, UTMD-mediated miR-205 delivery may be a promising method for the treatment of PCa.

Ultrasound‑targeted microbubble destruction‑mediated miR‑767 inhibition suppresses tumor progression of non‑small cell lung cancer

“…Ji et al (38) investigated the application of UTMD in miR-133a delivery and found that UTMD-mediated miR-133a inhibited tumor growth and improved the survival rate in a breast cancer mouse model, suggesting the therapeutic potential of UTMD-mediated miR-133a for breast cancer treatment. UTMD successfully enhanced the transfer of miR-205, as evidenced by the significant increase in miR-205 expression in prostate cancer cells, leading to suppressed tumor cell proliferation, migration and invasion and enhanced cell apoptosis (39). However, to the best of our knowledge, the application of UTMD in the treatment of NSCLC has rarely been reported.…”

miR-205: A Potential Biomedicine for Cancer Therapy

“…Moreover, ectopic expression of miR-205 increased the apoptotic dead cells (PI and Annexin V positive) after cisplatin treatment from 5.42% (Cisplatin alone) to 26.88% (Cisplatin + UTMD mediated miR-205). Additionally, cisplatin’s ability to inhibit the cellular migration was further enhanced with miR-205 [ 201 ]. In cisplatin resistant glioma cells, overexpression of miR-205 reversed the drug resistance via targeting E2F1.…”

tRNALys-Derived Fragment Alleviates Cisplatin-Induced Apoptosis in Prostate Cancer Cells

“…sncRNAs are also involved in the development of platinum-based drug resistance in prostate cancer [ 33 ]. In prostate cancer cells, miR-205 enhances cisplatin toxicity through the induction of cleaved caspase-9 and cytochrome c [ 9 ]. In addition, a miR-425-5p mimic suppresses the expression of cyclin D1 and targets GSK3β, to increase the sensitivity of prostate cancer cells to cisplatin [ 11 ].…”

“…In addition, studies over the past 20 years have demonstrated the possibility of using sncRNAs as biomarkers for the early diagnosis of cancer [ 8 ]. Moreover, sncRNAs regulate the sensitivity of cancer cells to anticancer agents [ 9 , 10 , 11 ].…”