Inhibitor of growth-4 is a potential target for cancer therapy

Yuan, Shuping; Jin, Jianhua; Shi, Juanjuan; Hou, Yongzhong

doi:10.1007/s13277-016-4842-3

Cited by 8 publications

(17 citation statements)

References 81 publications

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“… 8 Moreover, ING4 regulates the NF-κB signaling pathway by modifying gene transcription. 10 , 13 , 37 Therefore, we investigated whether ING4 could enhance the antitumor effect by inhibiting the NF-κB signaling. Consistent with previous reports, our results indicated that infection with oVV-ING4 downregulated the expression of components of the NF-κB family including p52/p100, p65, and p-p65 ( Figure 3B ) and induced apoptosis ( Figure 3A ).…”

Section: Discussionmentioning

confidence: 99%

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Peng¹,

Wang²,

Fan³

et al. 2018

OTT

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BackgroundIn consideration of the drug resistance and side effects associated with cytarabine, one of the most effective drugs for the treatment of acute myeloid leukemia (AML), there is a need for safer and effective strategies.MethodsIn the present investigation, we fabricated a new oncolytic vaccinia virus (oVV-ING4), which expresses the inhibitor of growth family member 4 (ING4) and explored its antitumor activity individually and in combination with cytarabine in AML cells.ResultsThe experiments confirmed that oVV can efficiently and specifically infect leukemia cells, and augment the ING4 gene expression. Flow cytometry and western blot demonstrated that oVV-ING4 enhances apoptosis and G2/M phase arrest in AML cells, and causes remarkable cancer cell death. In addition, the synergistic efficiency of oVV-ING4 and cytarabine was investigated in vitro and in vivo; the combination significantly inhibited the survival of leukemia cells in vitro and xenografted KG-1 AML tumor growth in vivo.ConclusionIn brief, oVV-ING4 can increase the sensitivity of leukemia cells to cytarabine and induce cell apoptosis in vitro and in vivo. Thus, oVV-ING4 may be a promising therapeutic candidate for leukemia and in combination with cytarabine represents a potential antitumor therapy.

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Section: Discussionmentioning

confidence: 99%

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Peng¹,

Wang²,

Fan³

et al. 2018

OTT

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“… 19 At that respect, delivery of ING4 gene via adenoviral vectors into HCC, 20 , 21 lung carcinoma, 22 colorectal cancer, 23 osteosarcoma, 24 hypopharngeal cancer 25 and other modalities human cancers, was found to not only inhibit tumor growth, angiogenesis and invasion, but also regulate cell proliferation and apoptosis and facilitate tumor cell sensitivity to other adjuvant anticancer agents. 19 , 20 , 21 , 22 , 23 , 24 , 25 Nevertheless, most of these previous trials were based on using the traditional replication-deficient adenoviral vector to deliver ING4 gene, and their data were collectively highlighted the importance of combining ING4 gene with additional antitumor gene or chemotherapeutic drugs to achieve more potent antitumor effects than ING4 gene-based monotherapy. 19 , 20 , 21 , 22 , 23 , 24 , 25 By far, the utility and usefulness of ING4 in gene virotherapy strategy is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: first evidence in preclinical hepatocellular carcinoma

El-Shemi

Ashshi

et al. 2017

Gene Ther

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Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4), as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as a potent apoptosis-inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono- and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-ΔB/TRAIL and/or Ad-ΔB/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-ΔB/ING4 plus Ad-ΔB/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-ΔB/ING4 and Ad-ΔB/TRAIL were remarkably cooperated to induce antitumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-ΔB/ING4 and Ad-ΔB/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation.

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“…7 A previous study reported that ING4 expression is positive in only 82.3% of the ccRCC renal tissues but in all of the normal renal tissues. 7 A previous study reported that ING4 expression is positive in only 82.3% of the ccRCC renal tissues but in all of the normal renal tissues.…”

Section: Discussionmentioning

confidence: 95%

“…6 Besides, the ING proteins also function as type I TSGs as they are found to be involved in DNA replication and repair. 7 In addition, ING4 also elevates the sensitivity to chemotherapy and radiotherapy in cancer cells. 7 In addition, ING4 also elevates the sensitivity to chemotherapy and radiotherapy in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…6 Previous studies proved that ING4 suppresses tumor growth, invasion, and metastasis. 7 ING4 loss is observed in many types of cancers, such as hepatocellular carcinoma, gastric, ovarian, colon, and breast cancers. 7 ING4 loss is observed in many types of cancers, such as hepatocellular carcinoma, gastric, ovarian, colon, and breast cancers.…”

Section: Introductionmentioning

confidence: 99%

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Inhibitor of growth 4 inhibits cell proliferation, migration, and induces apoptosis of renal cell carcinoma cells

Sun

Xie

et al. 2018

J of Cellular Biochemistry

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The inhibitor of growth 4 (ING4) is known as a tumor suppressor. The expressions of ING4 were markedly reduced in human renal clear cell carcinoma (ccRCC) tissues. However, the role of ING4 in renal cell carcinoma (RCC) remains unknown. The aim of the current study was to detect the ING4 expression level and its potential role in human RCC cell lines. Our results showed that ING4 was lowly expressed in human RCC cell lines compared with that in proximal tubular cell line. Ectopic overexpression of ING4 inhibited the proliferation, migration, and invasion properties, and as well as prevented epithelial‐mesenchymal transition (EMT) phenotype of RCC cells. In addition, ING4 overexpression induced cell apoptosis and autophagy in RCC cells. Furthermore, ING4 overexpression suppressed the activation of PI3K/Akt pathway in RCC cells. The activator of PI3K/Akt, insulin‐like growth factor 1, abolished the effects of ING4 on RCC cells. These findings indicated that ING4 presented anticancer activity in RCC cells. The effects of ING4 on RCC cells were mediated by regulating the PI3K/Akt pathway. These findings suggested that ING4 could be used for gene therapy of RCC.

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Inhibitor of growth-4 is a potential target for cancer therapy

Cited by 8 publications

References 81 publications

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: first evidence in preclinical hepatocellular carcinoma

Inhibitor of growth 4 inhibits cell proliferation, migration, and induces apoptosis of renal cell carcinoma cells

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