Tackling breast cancer chemoresistance with nano-formulated siRNA

Jones, Steven K.; Merkel, Olivia M.

doi:10.1038/gt.2016.67

Cited by 28 publications

(14 citation statements)

References 82 publications

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“…Chemotherapy is currently widely used in breast cancer treatment ( 28 ). Despite its impressive therapeutic effect, drug resistance has become a hurdle in several clinical cases ( 29 , 30 ). miRNAs have emerged as pivotal regulators of tumorigen-esis, particularly in drug resistance of breast cancer ( 31 – 33 ).…”

Section: Discussionmentioning

confidence: 99%

NT21MP negatively regulates paclitaxel-resistant cells by targeting miR‑155‑3p and miR‑155-5p via the CXCR4 pathway in breast cancer

et al. 2018

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Evidence has shown that microRNAs (miRNAs) are vital in cell growth, migration, and invasion by inhibiting their target genes. A previous study demonstrated that miRNA (miR)-155-3p and miR-155-5p exerted opposite effects on cell proliferation, apoptosis, migration and invasion in breast cancer cell lines. An miRNA microarray was used to show that miR-155-3p was downregulated whereas miR-155-5p was upregulated in paclitaxel-resistant (PR) cells compared with parental breast cancer cells. However, the role of miR-155 in breast cancer cell invasion and metastasis remains to be elucidated. A 21-residue peptide derived from the viral macrophage inflammatory protein II (NT21MP), competes with the ligand of CXC chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1α, inducing cell apoptosis in breast cancer. The present study aimed to identify the underlying mechanism of action of miR-155-3p/5p and NT21MP in PR breast cancer cells. Quantitative polymerase chain reaction, western blotting, wound-healing, cell cycle and apoptosis assays, and Cell Counting kit-8 assay were used to achieve this goal. The combined overexpression of miR-155-3p with NT21MP decreased the migration and invasion ability and increased the number of apoptotic and arrested cells in the G0/G1 phase transition in vitro. The knockdown of miR-155-5p combined with NT21MP had a similar effect on PR breast cancer cells. Furthermore, the ectopic expression of their target gene myeloid differentiation primary response gene 88 (MYD88) or tumor protein 53-induced nuclear protein 1 (TP53INP1) combined with NT21MP enhanced the sensitivity of the breast cancer cells to paclitaxel. Taken together, these findings suggested that miR-155-3p/5p and their target genes MYD88 and TP53INP1 may serve as novel biomarkers for NT21MP therapy through the CXCR4 pathway for improving sensitivity to paclitaxel in breast cancer.

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Section: Discussionmentioning

confidence: 99%

NT21MP negatively regulates paclitaxel-resistant cells by targeting miR‑155‑3p and miR‑155-5p via the CXCR4 pathway in breast cancer

et al. 2018

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“…Due the advances on molecular oncology, in the past 20 years, we increased our knowledge regarding posttranscriptional mechanisms involved in gene regulation, including microRNAs and long noncoding RNAs [ 76 ]. Since several alterations associated with BC resistance are associated with posttranscriptional regulation, the discovery of RNA interference or small-interfering RNAs (siRNAs) brought a new therapeutic perspective [ 76 , 77 ]. siRNA is considered more specific than tyrosine kinase inhibitors, and the association of siRNA with drug delivery systems can revolutionize BC treatment.…”

Section: Emerging Targets For Treatmentmentioning

confidence: 99%

Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems

et al. 2020

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Breast cancer (BC) is one of the most important cancers worldwide, and usually, chemotherapy can be used in an integrative approach. Usually, chemotherapy treatment is performed in association with surgery, radiation or hormone therapy, providing an increased outcome to patients. However, tumors can develop resistance to different drugs, progressing for a more aggressive phenotype. In this scenario, the use of nanocarriers could help to defeat tumor cell resistance, providing a new therapeutic perspective for patients. Thus, this systematic review aims to bring the molecular mechanisms involved in BC chemoresistance and extract from the previous literature information regarding the use of nanoparticles as potential treatment for chemoresistant breast cancer.

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“…[5–7] Resistance mechanisms often include an increase in anti-apoptotic proteins, increase in drug efflux pumps, or altered drug targets. [8–15] Once patients experience chemoresistance, treatment options become considerably limited.…”

Section: Introductionmentioning

confidence: 99%

Correlating quantitative tumor accumulation and gene knockdown using SPECT/CT and bioluminescence imaging within an orthotopic ovarian cancer model

et al. 2018

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Using an orthotopic model of ovarian cancer, we studied the delivery of siRNA in nanoparticles of tri-block copolymers consisting of hyperbranched polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hyPEI-g-PCL-b-PEG) with and without a folic acid targeting ligand. A SKOV-3/LUC FRα overexpressing cell line was employed to mimic the clinical manifestations of ovarian cancer. Both targeted and non-targeted micelleplexes were able to effectively deliver siRNA to the primary tumor and its metastases, as measured by gamma scintillation counting and confocal microscopy. Stability of the micelleplexes was demonstrated with a serum albumin binding study. Regarding biodistribution, intravenous (I.V.) administration showed a slight advantage of FRα targeted over non-targeted micelleplex accumulation within the tumor. However, both formulations displayed significant liver uptake. On the other hand, intraperitoneally (I.P.) injected mice showed a modest 6% of the injected dose per gram (ID/g) uptake within the primary and most interestingly also in the metastatic lesions which subsequently resulted in a 62% knockdown of firefly luciferase expression in the tumor after a single injection. While this is, to the best of our knowledge, the first paper that correlates quantitative tumor accumulation in an orthotopic tumor model with in vivo gene silencing, these data demonstrate that PEI-g-PCL-b-PEG-Fol conjugates are a promising option for gene knockdown in ovarian cancer.

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Tackling breast cancer chemoresistance with nano-formulated siRNA

Cited by 28 publications

References 82 publications

NT21MP negatively regulates paclitaxel-resistant cells by targeting miR‑155‑3p and miR‑155-5p via the CXCR4 pathway in breast cancer

NT21MP negatively regulates paclitaxel-resistant cells by targeting miR‑155‑3p and miR‑155-5p via the CXCR4 pathway in breast cancer

Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems

Correlating quantitative tumor accumulation and gene knockdown using SPECT/CT and bioluminescence imaging within an orthotopic ovarian cancer model

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