Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo

Mao, Zonglei; He, Songbing; Sheng, Wei; Dong, Xiaoqiang; Yang, Jicheng

doi:10.3892/or.2013.2671

Cited by 8 publications

(5 citation statements)

References 44 publications

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Furthermore, Ad-ING4 plus cisplatin combined treatment resulted in synergistic growth inhibition, enhanced apoptosis and reduced tumor vessel CD34 expression and microvessel density (MVD) in hepatocarcinoma cells [90]. This combined treatment could also reverse multidrug resistance and induce apoptosis of cisplatin-resistant gastric cancer cells in vitro and in vivo [91]. ING4 was also involved in the regulation of docetaxel (DTX) sensitivity in human lung adenocarcinoma (LAD).…”

Section: Ing4 In Cancer Therapymentioning

confidence: 99%

The Emerging Role of Inhibitor of Growth 4 as a Tumor Suppressor in Multiple Human Cancers

Cui

Gao

Zhang

et al. 2015

Cell Physiol Biochem

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Inhibitor of growth 4 (ING4), a member of the conserved ING family, has been identified as an important tumor suppressor since it plays a critical role in the regulation of chromatin modification, cell proliferation, angiogenesis and cell migration. Some observations suggest that ING4 acts as a key regulator of tumorigenesis through modifying gene transcription in part by regulating the transcription factors p53 and NF-kappaB (NF-κB). However, these models have yet to be substantiated by further investigations. Numerous reports describe the reduced expression of ING4 in cancers, and the responsible mechanisms are involved in gene deletion, mutation, transcriptional and post-transcriptional dysregulation. This review aims to summarize the recent published literature that investigates the role of ING4 in regulating tumorigenesis and progression, and explore its potential for cancer treatment.

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“…ING4 is proven to be a modulator of docetaxel (DTX) and paclitaxel sensitivity to overcome drug resistance in human lung adenocarcinoma and colorectal cancer [91,105]. Ad-ING4 reverses gastric cancer MDR in vitro and in vivo via the down-regulation of ATP-binding cassette transporters and activation of apoptotic pathways [131]. In addition to chemotherapies, radiotherapy is also an important tool in the treatment of cancers.…”

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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Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo

Cited by 8 publications

References 44 publications

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

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

The Emerging Role of Inhibitor of Growth 4 as a Tumor Suppressor in Multiple Human Cancers

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

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