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MiRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy.

ABSTRACT: The therapeutic application of microRNA(s) in the field of cancer has generated significant attention in research. Previous studies have shown that miR-205 negatively regulates prostate cancer cell proliferation, metastasis, and drug resistance. However, the delivery of miR-205 is an unmet clinical need. Thus, the development of a viable nanoparticle platform to deliver miR-205 is highly sought. A novel magnetic nanoparticle (MNP)-based nanoplatform composed of an iron oxide core with poly(ethyleneimine)-poly(ethylene glycol) layer(s) was developed. An optimized nanoplatform composition was confirmed by examining the binding profiles of MNPs with miR-205 using agarose gel and fluorescence methods. The novel formulation was applied to prostate cancer cells for evaluating cellular uptake, miR-205 delivery, and anticancer, antimetastasis, and chemosensitization potentials against docetaxel treatment. The improved uptake and efficacy of formulations were studied with confocal imaging, flow cytometry, proliferation, clonogenicity, Western blot, q-RT-PCR, and chemosensitization assays. Our findings demonstrated that the miR-205 nanoplatform induces significant apoptosis and enhancing chemotherapeutic effects in prostate cancer cells. Overall, these study results provide a strong proof-of-concept for a novel nonviral-based nanoparticle protocol for effective microRNA delivery to prostate cancer cells.

SUBMITTER: Nagesh PKB

PROVIDER: S-EPMC6162422 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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miRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy.

Nagesh Prashanth K B PKB Chowdhury Pallabita P Hatami Elham E Boya Vijaya K N VKN Kashyap Vivek K VK Khan Sheema S Hafeez Bilal B BB Chauhan Subhash C SC Jaggi Meena M Yallapu Murali M MM

Cancers 20180825 9

The therapeutic application of microRNA(s) in the field of cancer has generated significant attention in research. Previous studies have shown that miR-205 negatively regulates prostate cancer cell proliferation, metastasis, and drug resistance. However, the delivery of miR-205 is an unmet clinical need. Thus, the development of a viable nanoparticle platform to deliver miR-205 is highly sought. A novel magnetic nanoparticle (MNP)-based nanoplatform composed of an iron oxide core with poly(ethyl ...[more]

PMID: 30149628

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Project description:Background:The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods:The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results:The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion:miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.

Project description:Background:The aim of the study was to evaluate whether the use of chemotherapy in combination with naringin, a dietary plant polyphenolic flavonoid, could enhance the therapeutic efficacy of paclitaxel treatment in human prostate cancer (PCa) cells. Materials and methods:DU145, PC3, and LNCaP cells were treated with various concentrations of paclitaxel, naringin, and their combinations. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), image-based cytometer, quantitative reverse transcription PCR (RT-qPCR), Western blot, and transwell assay were used to evaluate cell viability, apoptosis and cell cycle, the mRNA expression, protein expression, and cell migration, respectively. Results:Naringin treatment inhibited cell survival in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest in G1 phase. Among the pathways evaluated, naringin (150 ?M) significantly induced the mRNA expressions of BAX, BID, caspase 3, cytochrome c, p53, p21 Cip1 , and p27 Kip1 and downregulated the expressions of survivin and livin in DU145 cells. The combination of naringin and paclitaxel treatments synergistically increased the cytotoxic effects of paclitaxel in androgen-independent DU145 and PC3 cells, as well as in androgen-sensitive LNCaP cells. The combination of naringin with docetaxel has almost the same inhibitory effect on cell proliferation as the paclitaxel combination in androgen-independent cells, whereas there is no similar effect in LNCaP cells. Naringin exhibits significant inhibitory effects on the cell migration ability. The flavonoid either alone or in combination with paclitaxel therapy resulted in an increase in tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) protein expression and decrease in nuclear factor-?B p50 protein level in DU145 cells. Conclusion:In conclusion, naringin acts as a chemosensitizer which synergistically strengths the cytotoxic effect of paclitaxel in PCa cells. Therefore, naringin therapy alone or in combination with paclitaxel may be useful in the treatment of PCa. However, there is a need for more detailed in vivo studies of the mechanism of action.

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MiRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy.

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miRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy.

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