4.5 Article

Cobalt chloride-stimulated hypoxia promotes the proliferation of cholesteatoma keratinocytes via the PI3K/Akt signaling pathway

期刊

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
卷 18, 期 15, 页码 3403-3411

出版社

IVYSPRING INT PUBL
DOI: 10.7150/ijms.60617

关键词

hypoxia; cholesteatoma; HIF-1 alpha; cell proliferation; PI3K/Akt signaling pathway

资金

  1. Science Project of Shanghai Municipal Health Bureau [20174Y0062]

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Hypoxia induces proliferation of cholesteatoma keratinocytes through upregulating p-PDK1 and p-Akt expressions via the PI3K-Akt signaling cascade. Inhibition of p-Akt expression by specific inhibitor LY294002 significantly reduces hypoxia-induced cell proliferation in cholesteatoma keratinocytes. This study provides evidence supporting the involvement of hypoxia in cholesteatoma initiation and progression.
Herein, we purposed to explore whether hypoxia triggers proliferation of cholesteatoma keratinocytes via the PI3K-Akt signaling cascade. Cells were inoculated with different concentration of CoCl2. The proliferation and cellular HIF-1 alpha, p-PDK1 and p-Akt expression levels of cholesteatoma keratinocytes were assessed in vitro. Hypoxia escalated cell proliferation via upregulating p-PDK1 and p-Akt expressions. Specific inhibitor of the PI3K-Akt signaling cascade, LY294002 markedly inhibited the expression of p-Akt and significantly reduces the hypoxia-induced proliferation of cholesteatoma keratinocytes. Our data provides research evidence confirming that hypoxia participates in the onset and progress of cholesteatoma.

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