Primary or acquired resistant mechanisms prevent the employment of individualized therapy with target drugs like the mTOR inhibitor everolimus (EVE) in hepatocellular carcinoma (HCC). The current study evaluated the effect of 1,25(OH)Vitamin D (VitD) treatment on EVE sensitivity in established models of HCC cell lines resistant to everolimus (EveR). DNA content and colony formation assays, which measure the proliferative index, revealed that VitD pre-treatment re-sensitizes EveR cells to EVE treatment. The evaluation of epithelial and mesenchymal markers by western blot and immunofluorescence showed that VitD restored an epithelial phenotype in EveR cells, in which prolonged EVE treatment induced transition to mesenchymal phenotype. Moreover, VitD treatment prompted hepatic miRNAs regulation, evaluated by liver miRNA finder qPCR array. In particular, miR-375 expression was up-regulated by VitD in EveR cells, in which miR-375 was down-regulated compared to parental cells, with consequent inhibition of oncogenes involved in drug resistance and epithelial-mesenchymal transition (EMT) such as MTDH, YAP-1 and c-MYC. In conclusion, the results of the current study demonstrated that VitD can re-sensitize HCC cells resistant to EVE treatment triggering miR-375 up-regulation and consequently down-regulating several oncogenes responsible of EMT and drug resistance.
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http://dx.doi.org/10.1038/s41598-019-48081-9 | DOI Listing |
Cell Commun Signal
December 2024
EV group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Viikinkaari 9, Helsinki, 00790, Finland.
Background: Beyond their conventional roles in hemostasis and wound healing, platelets have been shown to facilitate hematogenous metastasis by interacting with cancer cells. Depending on the activation route, platelets also generate different platelet-derived extracellular vesicles (PEVs) that may educate cancer cells in the circulation or within the tumor microenvironment. We engaged different platelet-activating receptors, including glycoprotein VI and C-type lectin-like receptor 2, to generate a spectrum of PEV types.
View Article and Find Full Text PDFPain Physician
December 2024
Department of Anesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, China.
Background: Visceral pain is common in cesarean sections conducted under combined spinal-epidural anesthesia (CSE). Epidural volume extension (EVE) is a technique for enhancing the effect of intrathecal blocks by inducing epidural fluid boluses in the CSE. Whether EVE that uses different drugs can reduce visceral pain during cesarean sections is rarely studied.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea.
Steroids, which are often used to treat the inflammation associated with various skin diseases, have several negative side effects. As extract has anti-inflammatory effects in various diseases, we evaluated the efficacy of -derived extracellular vesicles (EVEs) in decreasing 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. We determined the effect of the EVEs on the TLR4/NF-κB/NLRP3 inflammasome in human keratinocytes and mouse ear skin.
View Article and Find Full Text PDFBreast cancer is the leading cancer among women, with a significant number experiencing recurrence and metastasis, thereby reducing survival rates. This study focuses on the role of long noncoding RNAs (lncRNAs) in breast cancer immunotherapy response. We conducted an analysis involving 1027 patients from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, and The Cancer Genome Atlas, utilizing RNA sequencing and pathology whole-slide images.
View Article and Find Full Text PDFNat Genet
December 2024
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-cell transcriptomes of 232,080 cells and spatially resolved transcriptomes of tumors from 19 patients before and after ICB-chemotherapy. We find that tumor cells and secreted phosphoprotein 1-positive macrophages interact with collagen type XI alpha 1 chain-positive cancer-associated fibroblasts to stimulate the deposition and entanglement of collagen fibers at tumor boundaries, obstructing T cell infiltration and leading to poor prognosis.
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