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. 2023 Aug 1;14(8):488. doi: 10.1038/s41419-023-06009-2

Fig. 6. Targeting HK2 could alleviate radio-resistance.

Fig. 6

A CCK8 assays of Keto (20 μM, 48 h) with or without 8 Gy radiation and and the Q-value of the combination index of IR and Keto, respectively (n = 3). B Western blotting of apoptosis-related protein including Cyto c, Cleaved Caspase 3, and Caspase 3 in indicated groups with or without 8 Gy radiation. C Diagram of mice subcutaneous xenograft models with IR or Keto. D–F Tumor growth rate and tumor images of subcutaneous xenograft models in indicated mice with indicated cells and treatments. G, H Representative IHC staining of PCNA, Cyto c, LC3 II, and HK2 in the formalin-fixed tumor sections from nude mice and C57 mice with H22 LV-HK2 groups. Scale bar 20 μm. I–L Mice weight and indicators of mice liver and kidney in nude mice (n = 6) and C57 mice (n = 5) with H22 LV-HK2 groups. The units of ALT and AST are U/L. The units of UREA and CREA are Mmol/L and μmol/L, respectively. M–P Representative IHC staining and qualification of CD8, CD163, and CD206 in the formalin-fixed tumor sections from C57 mice with H22 LV-HK2 groups (n = 5). Scale bar 40 μm. Q Schematic diagram summarizing our working model, in brief, HK2 could interact with and prompt the lysosomal-dependent autophagy of AIMP2, thereby attenuating radiation-induced apoptosis, while high HK2 expression promotes immunosuppression, both of which accelerate the progression of HCC. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.