High concentration of γ-H2AX correlates with a marker of apoptotic suppression and PI3K/Akt pathway upregulation in glioblastoma multiforme

Glioblastoma multiforme (GBM) is a very aggressive type of primary brain tumor in adults with a poor prognosis. DNA double-strand breaks are known to be associated with the development of numerous cancer types due to their ability to generate genomic instabilities. In GBM, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a common pathway that can be activated by exogenous and endogenous factors. Genomic instability may be an endogenous stimulating factor for activation of the PI3K/Akt pathway, which may inhibit the apoptosis of GBM cells. Spontaneous DNA double-strand breaks play an essential role in the survival of GBM cells, and apoptosis levels may reflect survival ability. However, no study has yet been conducted to analyse the association between spontaneous DNA double-strand breaks and apoptosis in patients with GBM prior to treatment. Therefore, the present study examined the concentrations of gamma-histone 2AX (gamma-H2AX), a sensitive marker of spontaneous DNA double-strand breaks, and cleaved caspase-3, a marker of apoptosis, in patients with GBM. The correlation of gamma-H2AX with cleaved caspase-3, PI3K and Akt was also investigated. A total of 26 pre-treatment tumor tissue specimens from patient with GBM were analyzed to determine the concentrations of gamma-H2AX, PI3K, Akt and cleaved caspase-3 using sandwich enzyme-linked immunosorbent assays. The results showed a moderate positive correlation between gamma-H2AX and PI3K (r=0.52; P=0.007), a moderate positive correlation between gamma-H2AX and Akt (r=0.4; P=0.041) and a strong negative correlation between gamma-H2AX and cleaved caspase-3 (r=-0.61; P=0.0009). These analyses were also performed in seven tumor tissue specimens from patients with grade I glioma as controls, but no significant correlations were detected. The findings of the present study suggest that a high level of gamma-H2AX may affect GBM cell apoptosis via the PI3K/Akt pathway.

Automated summary

This study investigated the concentrations of gamma-H2AX and cleaved caspase-3 in patients with GBM, as well as their correlations with PI3K and Akt. The results showed a moderate positive correlation between gamma-H2AX and PI3K, a moderate positive correlation between gamma-H2AX and Akt, and a strong negative correlation between gamma-H2AX and cleaved caspase-3. Therefore, gamma-H2AX may affect GBM cell apoptosis via the PI3K/Akt pathway.