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. 2023 Oct 6;14(10):652. doi: 10.1038/s41419-023-06171-7

Fig. 8. PI3K/mTOR inhibitors overcome the radioresistance of SCLC in vivo.

Fig. 8

A–D The cell proliferation of two murine SCLC cell lines (TKO-tdTomato and TKO-mTmG) treated with different treatments were determined by CCK8 assay. E The HE staining of the whole lung in TKO mice from various groups was performed. F The tumor area/area of the lung in TKO mice from various groups was quantitatively calculated. G, H The volume and weight of allograft tumors in TKO mice treated with PI3K/mTOR inhibitors combined with or without IR was detected. I The expression of Ki67 in allograft tumor samples from TKO mice in different groups were determined by IHC. J PI3K/AKT/mTOR pathway promoted SCLC radioresistance by regulating the pentose phosphate pathway, and PI3K/mTOR inhibitors overcome SCLC radioresistance through increasing ROS level and reducing G6PD expression. PI3K/mTOR inhibitors promoted the interaction between G6PD and HSPA8/HSC70, and accelerated G6PD degradation through chaperone-mediated autophagy process.