Targeted Inhibition of miR-221/222 Promotes Cell Sensitivity to Cisplatin in Triple-Negative Breast Cancer MDA-MB-231 Cells

Cisplatin has been widely used in the treatment of a various types of cancers including triple-negative breast cancer (TNBC) by damaging DNA and inducing apoptosis. However, its anti-cancer effects are often limited due to chemo-resistance, which is one of the main reasons causing cancer relapse and metastasis. To overcome resistance, cisplatin is often used in combination with other drugs or molecules. Our study found that the targeted inhibition of miR-221/222 in MDA-MB-231 cells promoted cisplatin-induced cell apoptosis, and increased the cell sensitivity to cisplatin in vitro. Much higher expression levels of miR-221/222 were detected in the cisplatin-resistant MDA-MB-231 cells and in cisplatin-resistant breast cancer patients. The combination chemotherapy of cisplatin with anti-miR-221/222 showed much higher efficiency in suppressing tumor growth in the mice transplanted with MDA-MB-231 cells. In addition, anti-miR-221 and anti-miR-222 showed synergetic effects on improving sensitivity to cisplatin in MDA-MB-231 cells. Suppression of SOCS1-STAT3-Bcl-2 pathway and activation of p53-Pten signaling both contribute to anti-miR-221/222-induced sensitivity to cisplatin in MDA-MB-231 cells. These findings suggest the potential of a novel approach for the combination chemotherapy of cisplatin with small non-coding RNA in treatment of human TNBC.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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In conclusion, this study suggests that epigenetic age acceleration is significantly associated with lung function in women older than 50 years. We hypothesised that this could be due to menopause. However, we have observed that menopause has minimal effect and therefore there is possibility of other unknown physiological factors at older age in females mediating the epigenetic age acceleration effect on lung function. While, it is still unknown what exactly epigenetic aging from DNA methylation measures, this study suggests it can be utilised as one of the important factors to assess women's lung health in old age. DNA me...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we enriched populations of chemoresistant cancer stem cells from breast cancer and non-transformed breast cell lines using mammospheres. These mammospheres were treated or not with two chemoreagents, and we profiled surviving cells using miRNA microarray analysis. Comparison of the profiles from treated and untreated mammospheres as well as control and cancer cells yielded a six-miRNAs signature specific for chemoresistant stem cell-enriched subpopulations. From this signature miR-363-3p was found to be most highly overexpressed in various breast cancer cell lines and derived cancer stem cell-enriched popula...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by array Homo sapiens Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The accumulation of lingering senescent cells is an important contributing cause of degenerative aging. In this intriguing report, researchers note that senescent cells resulting from chemotherapy treatment can consume neighboring cells in order to prolong their survival. This is most likely the case for senescent cells in general, whatever their origin. This cellular cannibalism is probably detrimental to tissue function to some small degree, but, since senescent cells are always a tiny minority of all cells, even in old tissues, it is nowhere near as detrimental as the inflammatory signaling profile that accompanies cell...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Drug Res (Stuttg) DOI: 10.1055/a-0892-4118HER2-positive breast tumors are found in 25–30% of patients with breast cancer and are characterized by aggressive course and reduced sensitivity to both chemotherapy and hormone therapy. The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse. Male FBV/N mice with intramuscularly transplanted HER2-positive mammary gland tumor from a female mouse of the same strain have been given toremifene (30...
Source: Drug Research - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research
ConclusionsThis case reports shows that MNC IVF conception after OTC is successful in patients with tissue partially placed in a peritoneal window. If the tissue placed in the peritoneal window becomes active, MNC IVF can be performed. If the tissue placed in the remaining ovary becomes active, natural conception should be pursued.
Source: Case Reports in Womens Health - Category: OBGYN Source Type: research
er Lukowski KCa3.1 K+ channels reportedly contribute to the proliferation of breast tumor cells and may serve pro-tumor functions in the microenvironment. The putative interaction of KCa3.1 with major anti-cancer treatment strategies, which are based on cytotoxic drugs or radiotherapy, remains largely unexplored. We employed KCa3.1-proficient and -deficient breast cancer cells derived from breast cancer-prone MMTV-PyMT mice, pharmacological KCa3.1 inhibition, and a syngeneic orthotopic mouse model to study the relevance of functional KCa3.1 for therapy response. The KCa3.1 status of MMTV-PyMT cells did not determine...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We examined the impact of total body irradiation (TBI) dose and fractionation on risk of subsequent malignant neoplasms (SMNs) in the era of reduced-intensity and nonmyeloablative conditioning regimens for hematopoietic cell transplantation (HCT). Among 4905 1-year survivors of allogeneic HCT for hematologic malignancies (N = 4500) or nonmalignant disorders (N = 405) who received transplants between 1969 and 2014, we identified 581 SMNs (excluding squamous and basal cell of skin) in 499 individuals. With a median length of follow-up of 12.5 years, the cumulative incidence of SMNs by 30 years after HCT was 22.0%. Compared w...
Source: Blood - Category: Hematology Authors: Tags: Transplantation, Clinical Trials and Observations Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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