The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl<sub>2</sub>, which inhibited the aquaporin-9/AKT signaling.<h4>Conclusion</h4>Overall, these findings underscore the importance of H<sub>2</sub>O<sub>2</sub>-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance. Here, AKT1 is linked to glioblastoma.