Impact of targeting insulin-like growth factor signaling in head and neck cancers

Limesand, Kirsten H.; Chibly, Alejandro M.; Fribley, Andrew M.

doi:10.1016/j.ghir.2013.06.001

Cited by 22 publications

(26 citation statements)

References 65 publications

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“…EGFR amplification and over‐expression were found in more than 60% of primary glioblastomas, which leads to excitation of several signalling pathways, including PI3K/Akt and Ras/Raf/MAPK and subsequently proliferation, invasion and survival of tumour cells . Some reports have shown that expression of IRS‐1 and IRS‐2, two upstream modulators of IGF‐1R/Akt pathway, are elevated in various types of cancer cells . Other reports have demonstrated that Akt activity is regulated through a combination of EGFR and IGF‐1R pathways, and inhibition of EGFR causes the activation of the IGF‐1R pathway.…”

Section: Discussionmentioning

confidence: 99%

MiRNA-7 enhances erlotinib sensitivity of glioblastoma cells by blocking the IRS-1 and IRS-2 expression

Alamdari-Palangi

Amini

Karami

2020

Journal of Pharmacy and Pharmacology

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Objectives Down‐regulation of miRNA‐7 is correlated with over‐expression of IRS‐1 and IRS‐2 proteins, the upstream regulators of IGF‐1R/Akt pathway, in glioblastoma cells. In this study, the effect of miRNA‐7 on expression of IRS‐1 and IRS‐2 and sensitivity of the U373‐MG glioblastoma cells to erlotinib was explored. Methods After miRNA‐7 transfection, the expression of IRS‐1 and IRS‐2 mRNAs was measured by RT‐qPCR. Trypan blue assay was used to assess the effect of miRNA‐7 on cell proliferation. The effects of miRNA‐7 and erlotinib, alone and in combination, on cell survival and apoptosis were measured using MTT assay and ELISA cell death assay, respectively. Key findings Our data showed that miRNA‐7 markedly inhibited the expression of IRS‐1 and IRS‐2 in a time‐dependent manner, inhibited the proliferation of glioblastoma cells and enhanced apoptosis (P < 0.05, relative to control). Pretreatment with miRNA‐7 synergistically inhibited the cell survival rate and decreased the IC50 of erlotinib. Furthermore, miRNA‐7 significantly augmented the apoptotic effect of erlotinib. Conclusions Our data propose that inhibition of IRS‐1 and IRS‐2 by miRNA‐7 can effectively induce apoptosis and sensitize glioblastoma cell to EGFR‐TKIs. Therefore, miRNA‐7 may be a potential therapeutic target in patients with glioblastoma.

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Section: Discussionmentioning

confidence: 99%

MiRNA-7 enhances erlotinib sensitivity of glioblastoma cells by blocking the IRS-1 and IRS-2 expression

Alamdari-Palangi

Amini

Karami

2020

Journal of Pharmacy and Pharmacology

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“…Besides, some agents targeting IGF-1 signaling are also promising in the treatment of some cancers [13,35,36]. Other factors in the IGF system are also likely to be potential therapeutic targets, and anticancer therapies aiming to target those factors are currently under investigation [13,35,36].…”

Section: Discussionmentioning

confidence: 99%

Circulating Insulin-Like Growth Factor-1 Level and Ovarian Cancer Risk

Zhang²,

Zheng³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Insulin-like growth factor-1 (IGF-1) has an important role in cells' proliferation, differentiation and apoptosis, and it may be involved in carcinogenesis. Several epidemiological studies assessed the association between circulating IGF-1 level and ovarian cancer risk, but there was still no conclusive finding. Methods: A meta-analysis of published studies was performed to assess the association between circulating IGF-1 level and ovarian cancer risk. The summary odds ratio (OR) with 95% confidence interval (95%CI) was calculated through meta-analysis to evaluate the strength of the association. Results: Five eligible studies were included into the meta-analysis, which involved a total of 2,028 cases of ovarian cancer and 4,625 controls. Meta-analysis of total 5 studies showed that high circulating IGF-1 level was correlated with decreased risk of ovarian cancer (OR = 0.84, 95%CI 0.74-0.97, P = 0.013). After adjusting for heterogeneity, high circulating IGF-1 level was still correlated with decreased risk of ovarian cancer (OR = 0.83, 95%CI 0.72-0.95, P = 0.007). Subgroup analysis by age showed that circulating IGF-1 level was not correlated with ovarian cancer risk in women both less than 55 years and more than 55 years. However, after adjusting for heterogeneity, high circulating IGF-1 level was correlated with decreased ovarian cancer risk in women less than 55 years (OR = 0.82, 95%CI 0.72-0.94, P = 0.004). Conclusion: Our meta-analysis suggests that high circulating IGF-1 level may be correlated with decreased ovarian cancer risk, especially in women less than 55 years. More studies are needed to further assess the association between circulating IGF-1 level and ovarian cancer risk in the future.

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“…Each year new cases of xerostomia with a concomitant loss of salivary gland function result from radiation treatment for head and neck cancer (HNC) (Limesand et al 2013). Radiation is a primary or secondary therapeutic modality for head and neck cancer cases and results in acute and chronic salivary gland dysfunction in most patients (Vissink et al 2010), as well as oral complications such as xerostomia, increased dental caries, increased risk for oral infections, and malnutrition (Vissink et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor-1–Mediated DNA Repair in Irradiated Salivary Glands Is Sirtuin-1 Dependent

et al. 2016

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Ionizing radiation is one of the most common cancer treatments; however, the treatment leads to a wide range of debilitating side effects. In patients with head and neck cancer (HNC), the surrounding normal salivary gland is extremely sensitive to therapeutic radiation, and damage to this tissue results in various oral complications and decreased quality of life (QOL). In the current study, mice treated with targeted head and neck radiation showed a significant increase in double-stranded breaks (DSB) in the DNA of parotid salivary gland cells immediately after treatment, and this remained elevated 3 h posttreatment. In contrast, mice pretreated with insulinlike growth factor-1 (IGF-1) showed resolution of the same amount of initial DNA damage by 3 h posttreatment. At acute time points (30 min to 2 h), irradiated parotid glands had significantly decreased levels of the histone deactylase Sirtuin-1 (SirT-1) which has been previously shown to function in DNA repair. Pretreatment with IGF-1 increased SirT-1 protein levels and increased deacetylation of SirT-1 targets involved in DNA repair. Pharmacological inhibition of SirT-1 activity decreased the IGF-1-mediated resolution of DSB. These data suggest that IGF-1 promotes DNA repair in irradiated parotid glands through the maintenance and activation of SirT-1.

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Impact of targeting insulin-like growth factor signaling in head and neck cancers

Cited by 22 publications

References 65 publications

MiRNA-7 enhances erlotinib sensitivity of glioblastoma cells by blocking the IRS-1 and IRS-2 expression

MiRNA-7 enhances erlotinib sensitivity of glioblastoma cells by blocking the IRS-1 and IRS-2 expression

Circulating Insulin-Like Growth Factor-1 Level and Ovarian Cancer Risk

Insulin-Like Growth Factor-1–Mediated DNA Repair in Irradiated Salivary Glands Is Sirtuin-1 Dependent

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