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. 2018 Jun 12;9(45):27698–27707. doi: 10.18632/oncotarget.25498

Figure 1. Hypoxia induces resistance to mTOR inhibitors in prostate cancer cells.

Figure 1

(A) Expression of HIF1-a, pAkt, pS6 in C4-2AT6 cells under normoxia, acute hypoxia, chronic hypoxia. “Acute” indicates cells cultured under hypoxia in one day, and “Chronic” cells cultured under hypoxia over one month. Expression of pAkt, pS6 under chronic hypoxia was up-regulated. (B) LNCaP under chronic hypoxia also showed higher expression of pAkt and pS6 compared to under normoxia. (C) Inhibitory effects of exposure to NVP-BEZ235 (500 nM) or RAD001 (100nM) for 24 hours on HIF1-a, pAkt, and pS6 in C4-2AT6 cells. NVP-BEZ235 inhibited the expression of pAkt and pS6. RAD001 inhibited the expression of pS6. (D) C4-2 cells and C4-2AT6 cells under normoxia were treated with RAD001. Cell viability was measured by WST assay. C4-2AT6 cells showed greater sensitivity to NVP-BEZ235 than C4-2 cells. *p< 0.05 compared to C4-2 at the same dose. (E) The number of C4-2AT6 cells under normoxia and hypoxia 24hr or 48hr after administration of RAD001. RAD001 exhibited low cytotoxicity towards C4-2AT6 under chronic hypoxia. ** p<0.01 compared to intact C4-2AT6 cells. (F) The number of LNCaP cells under normoxia and hypoxia 48hr after administration of RAD001. ***p<0.001 compared to intact LNCaP cells. (G) Inhibitory effects of exposure to Torin-1 for 24 hours on pAkt, pS6 and p4EBP1 in C4-2AT6 cells. (H) The number of C4-2AT6 cells under normoxia and hypoxia 24hr or 48hr after administration of Torin-1.