Fig. 6

PER sensitizes established xenograft HK1⁻HK2⁺ liver tumors to HK2 knockdown/DPI combination therapy. a PER enhances the ability of the HK2 knockdown/DPI combination to retard the progression of Hep3B/shHK2^DOX tumor xenografts. When tumors reached 200 mm³ (day 0), xenografts were randomized into a control group and two treatment groups. The control mice (n = 7) were remained on the standard diet and were treated with vehicle. In the treatment groups, mice were placed on a DOX-supplemented diet (from day 0) and treated either with DPI (2 mg/kg, daily i.p. from day 3, n = 7) or with [DPI (2 mg/kg, daily i.p.) + PER (30 mg/kg, daily i.p), from day 3, n = 8]. b Representative images of tumor progression in three mice from each group in panel a. c Body weights of the mice in panel a bearing xenograft subcutaneous tumors, in response to the indicated treatments. d shHK2/DPI/PER treatment activates AMPKα and dephosphorylates S6 and elicits cleavage of caspase-3 and caspase-7. Hep3B/shHK2^DOX tumors from the indicated treatment groups were collected at day 15. Protein extracts from tissue homogenate supernatants were analyzed. e PER enhances the ability of the HK2 knockdown/DPI combination to retard the progression of HK1⁻HK2⁺ Huh7shHK2^DOX liver tumor xenografts. Experimental conditions are the same as those described in panel a (n = 6). f PER enhances the ability of the HK2 knockdown/DPI combination to retard the progression of HK1⁻HK2⁺ HepG2/shHK2^DOX liver tumor xenografts. Experimental conditions are the same as those described in panel a (n = 5). g HK2 knockdown/DPI/PER combination suppresses HepG2/shHK2^DOX tumor growth. Weights of HepG2/shHK2^DOX tumors after indicated treatments of the xenograft-bearing mice shown in panel f are shown. All data are expressed as means ± SEM. *P < 0.05. **P < 0.01. ***P < 0.001