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. 2020 Apr;72(4):531-538.
doi: 10.1111/jphp.13226. Epub 2020 Feb 5.

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

Vahab Alamdari-Palangi  1 , Razieh Amini  1 , Hadi Karami  1   2
Affiliations

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

Vahab Alamdari-Palangi et al. J Pharm Pharmacol. 2020 Apr.

Abstract

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.

Keywords: erlotinib; glioblastoma; insulin receptor substrate; miRNA-7; sensitivity.

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References

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