Experimental Studies on the Inhibition of Adenovirus-ING4-OSM Therapy on Nasopharyngeal Carcinoma Proliferation In Vitro and In Vivo

Han, Zeli; Zhou, Changjiang; Sun, Baochun; Yan, Qinghong; Zhang, Jinghong

doi:10.1007/s12013-014-0097-z

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Cancer gene therapy has attracted increasing attention in the past few years. ING4 was identified as a potent tumor suppressor gene and has been proven to be involved in carcinogenesis as well as tumor cell proliferation, migration and invasion 37. Ectopic expression of IL-24 induces growth arrest and apoptosis in malignant human cells but causes minimal lethality toward normal cells 38.…”

Section: Discussionmentioning

confidence: 99%

Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells

Qu¹,

Wang²,

Feng³

et al. 2019

IJN

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IntroductionCancer gene therapy requires both effective tumor suppressor genes and safe vectors that express target genes efficiently. Inhibitor of growth 4 (ING4) inhibits tumor growth via multiple pathways. Interleukin-24 (IL-24) also has tumor-suppressive activity against a broad spectrum of human cancers. Adenovirus (Ad) vectors exhibit high infection efficiency, but potential toxicity related to high doses of adenovirus has led to careful reconsideration of their use in human clinical trials. Antheraea pernyi silk fibroin (ASF) is a cytocompatible and biodegradable natural polymer, and it possesses Arg–Gly–Asp sequences exhibiting a high binding affinity and selectivity for αvβ3 and αvβ5 integrin receptors, which are overexpressed in tumor vessels and most tumor cells.MethodsIn this study, an Arg-Gly-Asp peptide-modified Ad vector coexpressing ING4 and IL-24 was constructed by homologous recombination of the dual gene coexpression transfer plasmid and RGD-modified pAdEasy-1 adenoviral backbone plasmid. The cationic ASF (CASF) was prepared by modifying ASF with low-molecular-weight PEI. The negatively charged Ad vector was modified with CASF to form a CASF/Ad complex.ResultsHuman hepatoma carcinoma SMMC-7721 cells and normal hepatic L-02 cells were infected with the CASF/Ad complex, which showed significantly higher infection efficiency than the naked Ad. The CASF/Ad complex could effectively mediate the expression of the target gene ING4 in SMMC-7721 cells and the secretion of the target gene IL-24 from SMMC-7721 cells, thus inducing apoptosis of hepatoma carcinoma SMMC-7721 cells. The viability of SMMC-7721 and L-02 cells infected with the CASF/Ad complex was further assessed, and it was found that the growth of SMMC-7721 cells was significantly inhibited but that the growth and proliferation of L-02 cells were not affected.ConclusionThe CASF/Ad complex constructed in this study, showing improved infection efficiency and enhanced suppressive effects on human hepatoma carcinoma SMMC-7721 cells, has the potential to reduce the dose of adenovirus and still maintain high infection efficiency and tumor inhibition.

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Section: Discussionmentioning

confidence: 99%

Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells

Qu¹,

Wang²,

Feng³

et al. 2019

IJN

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“…Instead, it was noted that the degree of reduction in ING4 expression correlated with the progression from low to high grades of osteosarcoma, according to the Enneking classification system for malignant bone tumors (P=0.002). ING4, a novel tumor suppressor of the ING family, has potential tumor-suppressing effects that are exerted through various signaling pathways, including tumorigenesis, cell cycle regulation, angiogenesis, cell apoptosis, DNA repair, migration and transcriptional regulation (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(37)(38)(39)(40)(41)(42)(43). These functions of ING4, which acts as an oncogene suppressor in numerous tumor types, have been identified repeatedly in vitro and in vivo (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(37)(38)…”

Section: Discussionmentioning

confidence: 99%

Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

et al. 2016

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Abstract. Osteosarcoma is the most prevalent type of primary malignant bone tumor. Inhibitor of growth 4 (ING4) has been demonstrated to function as a tumor suppressor through multiple pathways, and is its expression is understood to be suppressed or reduced in various malignancies. The present study aimed to investigate the expression of ING4 and to determine its prognostic value in osteosarcoma tissue. Formalin-fixed, paraffin-embedded tissue microarrays were analyzed, and contained 41 osteosarcoma specimens and 11 normal bone tissue specimens with duplicate cores. ING4 expression was evaluated by immunohistochemical staining. The association between ING4 expression in the osteosarcoma and normal bone tissues was analyzed, in addition to the association between ING4 expression and Enneking classification of the osteosarcoma tissues. A significant statistical difference was observed in the ING4 immunohistochemical staining score between the osteosarcoma and normal bone tissues (P<0.001). Furthermore, a significant negative correlation was detected between the ING4 immunohistochemical staining scores and the Enneking classification results of the 41 osteosarcoma tissues (P=0.002). Low expression of ING4 was observed in the osteosarcoma specimens, and this reduced expression of ING4 was negatively correlated with Enneking classification. Thus, the results of the present study indicate that ING4 may serve as a promising prognostic marker in osteosarcoma. IntroductionOsteosarcoma, the most common primary bone malignancy, accounts for ~20% of all bone tumors and ~5% of all pediatric tumors (1). Osteosarcoma has an overwhelming tendency for invasion and early metastasis (2). Although treatment with surgery and neoadjuvant chemotherapy appears to cure 60-70% of cases (3), the 5-year survival rate for patients with recurrent and metastatic osteosarcoma is only 20% (4,5). Research investigating the mechanism of osteosarcoma development has primarily focused on chromosomal abnormalities, genetic alterations of tumor suppressor genes, activation of oncogenes and dysregulation of major signaling pathways. However, the molecular events that lead to the development of osteosarcoma are not yet fully understood.Inhibitor of growth 4 (ING4) functions as a tumor suppressor, thus serving an inhibitory role during the generation and development of various types of tumor, including thyroid (6), gastric (7), lung (8) and breast cancer (9). ING4 physically interacts with and phosphorylates p65, a subunit of nuclear factor-κB (NF-κB), therefore suppressing the activity of NF-κB (10). The inhibition of NF-κB negatively regulates various target genes, including matrix metalloproteinase (MMP)-2, MMP-9, interleukin (IL)-6, IL-8, cyclooxygenase-2 and colony stimulating factor-3. The downregulation of these cytokines inhibits angiogenesis and tumor cell growth (11-15). In RKO colorectal cancer cells, ING4 expression was able to decrease the cell population in the S-phase of the cell cycle in a p53-dependent manner, as well as upregulate p21...

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“…Nevertheless, the combined CRAd-IL24 and CRAd-ING4 vectors demonstrate no synergistic effects exceeding the oncolytic potency of a single CRAD-IL24 vector [140]. In contrast, recombinant adenoviruses, co-expressing ING4 along with a single gene such as PTEN, P53 , or OSM , have shown a synergistic tumor-suppressive capacity in diverse cancers, including nasopharyngeal carcinoma, hepatocellular carcinoma, hypopharyngeal cancer, breast cancer, gastric cancer, and glioma, while simultaneously promoting chemosensitivity of hypopharyngeal cancer [141–148]. Furthermore, other oncolytic virus-mediated gene therapy has exhibited ubiquitous antitumor potential.…”

Section: Potential Approaches In Tumor Therapymentioning

confidence: 99%

The essential role of tumor suppressor gene ING4 in various human cancers and non-neoplastic disorders

Cheng

2019

Bioscience Reports

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Inhibitor of growth 4 (ING4), a member of the ING family discovered in 2003, has been shown to act as a tumor suppressor and is frequently down-regulated in various human cancers. Numerous published in vivo and in vitro studies have shown that ING4 is responsible for important cancer hallmarks such as pathologic cell cycle arrest, apoptosis, autophagy, contact inhibition, and hypoxic adaptation, and also affects tumor angiogenesis, invasion, and metastasis. These characteristics are typically associated with regulation through chromatin acetylation by binding histone H3 trimethylated at lysine 4 (H3K4me3) and through transcriptional activity of transcription factor P53 and NF-κB. In addition, emerging evidence has indicated that abnormalities in ING4 expression and function play key roles in non-neoplastic disorders. Here, we provide an overview of ING4-modulated chromosome remodeling and transcriptional function, as well as the functional consequences of different genetic variants. We also present the current understanding concerning the role of ING4 in the development of neoplastic and non-neoplastic diseases. These studies offer inspiration for pursuing novel therapeutics for various cancers.

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Experimental Studies on the Inhibition of Adenovirus-ING4-OSM Therapy on Nasopharyngeal Carcinoma Proliferation In Vitro and In Vivo

Cited by 7 publications

References 29 publications

<p>Cationic <em>Antheraea pernyi</em> Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells</p>

<p>Cationic <em>Antheraea pernyi</em> Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells</p>

Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

The essential role of tumor suppressor gene ING4 in various human cancers and non-neoplastic disorders

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