Hypoxia Enhances Glioma Resistance to Sulfasalazine-Induced Ferroptosis by Upregulating SLC7A11 via PI3K/AKT/HIF-1α Axis

Figure 4

Hypoxia promoted SLC7A11 expression via PI3K/AKT/HIF-1α pathway. (a) Cell viability curves at different concentrations of SAS for 24 h. PX-478 can reverse the enhanced SAS resistance induced by hypoxia. (b) The IC₅₀ of SAS in hypoxia with PX-478 group was obviously low than that of hypoxia group. The bar graph showed of 3 independent experiments. (c) Protein expression level of HIF-1α and SLC7A11 influenced by oxygen content and HIF-1α inhibitor PX-478 measured by western blot. PX-478 markedly decreased HIF-1α and SLC7A11 protein levels. (d) Protein expression level of PI3K, AKT, p-AKT, HIF-1α, and SLC7A11 influenced by oxygen content and AKT inhibitor MK-2206 measured by western blot. AKT inhibitor MK-2206 along with hypoxia attenuated the expression level of p-AKT, HIF-1α, and SLC7A11. (e) The relationship between HIF-1α and SLC7A11 expression level in TCGA. SLC7A11 was positively correlated with HIF-1α in 257 glioma tumor samples. and .

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