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      Genetically engineered drug rhCNB induces apoptosis and cell cycle arrest in both gastric cancer cells and hepatoma cells

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          Calcineurin B (CNB) is a regulatory subunit of calcineurin, and it has antitumor activity. In this study, we aimed to investigate the effect of recombinant human calcineurin B (rhCNB) on the proliferation of gastric cancer cells and hepatoma cells both in vitro and in vivo.

          Materials and methods

          Cell viability and cell proliferation were detected by MTT and BrdU assay. Flow cytometry, Western blot and immunohistochemistry were performed to determine rhCNB-induced apoptosis and cell cycle arrest. The antitumor activities of rhCNB were observed in mice tumor models.


          We demonstrated that rhCNB inhibits the proliferation of gastric cancer cells and hepatoma cells both in vitro and in vivo. We showed that the inhibition of cell proliferation by rhCNB is associated with apoptosis and cell cycle arrest in both tumor cell lines. Furthermore, we indicated that rhCNB promotes p53 protein expression, a potent proapoptotic factor. Meanwhile, we also exhibited that rhCNB decreases the expression of both cyclin B1 and CDK1 proteins, two proteins associated with G 2/M arrest.


          Together, these findings suggest that rhCNB markedly inhibits tumor growth and provides guidance for its drug development.

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          Most cited references 24

          • Record: found
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          Targeting CDK4 and CDK6: From Discovery to Therapy.

          Biochemical and genetic characterization of D-type cyclins, their cyclin D-dependent kinases (CDK4 and CDK6), and the polypeptide CDK4/6 inhibitor p16(INK4)over two decades ago revealed how mammalian cells regulate entry into the DNA synthetic (S) phase of the cell-division cycle in a retinoblastoma protein-dependent manner. These investigations provided proof-of-principle that CDK4/6 inhibitors, particularly when combined with coinhibition of allied mitogen-dependent signal transduction pathways, might prove valuable in cancer therapy. FDA approval of the CDK4/6 inhibitor palbociclib used with the aromatase inhibitor letrozole for breast cancer treatment highlights long-sought success. The newest findings herald clinical trials targeting other cancers.
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            Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation.

            The immunosuppressive drugs cyclosporin A (CsA) and FK506 both interfere with a Ca(2+)-sensitive T-cell signal transduction pathway, thereby preventing the activation of specific transcription factors (such as NF-AT and NF-IL2A) involved in lymphokine gene expression. CsA and FK506 seem to act by interaction with their cognate intracellular receptors, cyclophilin and FKBP, respectively (see ref. 11 for review). The Ca2+/calmodulin-regulated phosphatase calcineurin is a major target of drug-isomerase complexes in vitro. We have therefore tested the hypothesis that this interaction is responsible for the in vivo effects of CsA/FK506. We report here that overexpression of calcineurin in Jurkat cells renders them more resistant to the effects of CsA and FK506 and augments both NFAT- and NFIL2A-dependent transcription. These results identify calcineurin as a key enzyme in the T-cell signal transduction cascade and provide biological evidence to support the notion that the interaction of drug-isomerase complexes with calcineurin underlies the molecular basis of CsA/FK506-mediated immunosuppression.
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              Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance.

              Exosomes are extracellular signalosomes that facilitate eukaryotic intercellular communication under a wide range of normal physiological contexts. In malignancies, this regulatory circuit is co-opted to promote cancer cell survival and outgrowth. Tumour-derived exosomes (TDEs) carry a pro-EMT (epithelial-mesenchymal transition) programme including transforming growth factor beta (TGFβ), caveolin-1, hypoxia-inducible factor 1 alpha (HIF1α), and β-catenin that enhances the invasive and migratory capabilities of recipient cells, and contributes to stromal remodelling and premetastatic niche formation. The integrin expression patterns on TDEs appear to dictate their preferential uptake by organ-specific cells, implying a crucial role of this pathway in organotropic metastasis. Through the expression of immunomodulatory molecules such as CD39 and CD73, TDEs modify the immune contexture of the tumour microenvironment, which could have implications for immunotherapy. Hence, targeting TDE dysregulation pathways, such as the heparanase/syndecan-1 axis, could represent novel therapeutic strategies in the quest to conquer cancer.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                20 August 2018
                : 12
                : 2567-2575
                [1 ]Key Laboratory of Preclinical Pharmacology and Toxicology of Hainan Province, Hainan Medical College, Haikou 571199, China, fujian.hnmc@ 123456163.com
                [2 ]Key Laboratory of Tropical Diseases and Translational Medicine of the Ministry of Education & Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou 571199, China
                Author notes
                Correspondence: Jian Fu, Key Laboratory of Preclinical Pharmacology and Toxicology of Hainan Province, Hainan Medical College, XueYuan Road 3 #, Haikou 571199, People’s Republic of China, Email fujian.hnmc@ 123456163.com

                These authors contributed equally to this work

                © 2018 Guo et al. This work is published and licensed by Dove Medical Press Limited.

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Pharmacology & Pharmaceutical medicine

                p53, rhcnb, cell cycle arrest, apoptosis, tumor cells


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