Fig. 6. HBO increases tumour volume but promotes chemosensitization due to cell cycle progression and decreases stemness by inhibiting HIF1α/HIF2α-Sox2.

A GBM cells after HBO exposure had a low proportion of cells in the G₁ phase and a high proportion of cells in the G₂/M+S phase. B HIF-ko cells were cultured in 1% O₂ for 72 h, and the proportion of cells in the G₁ phase decreased and the proportion of cells in the G₂/M+S phase increased after dual HIF1α/HIF2α knockout. Moreover, the proportion of cells in the G₁ phase was lower and the proportion of cells in the G₂/M+S phase was higher in dual HIF1α/HIF2α-KO cells than in individual HIF1α- or HIF2α-KO cells. However, cell cycle changes were not significantly different between the HIF1α- or HIF2α-KO individual group and the empty vector control group. C There were no significant differences between the control and empty vector groups, but there was a decrease in the proportion of cells in the G₁ phase and an increase in the proportion of cells in the G₂/M+S phase after Sox2 knockout. D After Sox2 knockout in GBM cells, the proliferation rate increased (compared to control and empty vector cells). E A positive correlation was observed between Sox2 and CD133, CD9 and Nestin. F CD133, CD9 and Nestin levels decreased significantly after Sox2 knockout. G There were much higher late and total apoptosis rates after Sox2 knockout relative to the control. H GBM includes glioma stem cells and differentiated glioma cells. When these cells are cultured under hypoxia, HIF1α/HIF2α-Sox2 will become activated, thus promoting cell cycle arrest in the G₁ phase and stemness, leading to chemotherapy resistance. However, if these cells are exposed to HBO, HIF1α/HIF2α-Sox2 will be inhibited, thus inhibiting cell cycle arrest and stemness and promoting not only cell growth but also chemotherapy sensitivity. The P value was determined by an independent samples t-test between two groups or one-way ANOVA between at least three groups.