Fig. 7.

Metformin inhibits xenograft tumor growth through activation of ASK1. Tumors originating from SKOV3 cells reached 150–200 mm3 before treatment with NQDI-1, 200–600 mg/kg metformin, or a combination of NQDI-1 and metformin (n = 5 in each group). a The average tumor volume was diminished by different metformin doses (*P < 0.05 and **P < 0.01 versus control group). b The average tumor weights were measured (*P < 0.05 and **P < 0.01 versus control group). c-e NQDI-1 weakened the anti-tumor effect of metformin according to the change of tumor volume and weights (*P < 0.05 and **P < 0.01 versus control group; ^#P < 0.05 and ^##P < 0.01 versus metformin alone). f ASK1 and p-ASK1 levels according to western blot analysis of protein extracts from SKOV3 xenograft tumors (**P < 0.01 versus control group; ^##P < 0.01 versus metformin alone). g The expression of Grp78, GADD153 and cleaved caspase 3 was detected through immunohistochemistry in SKOV3 xenograft tumors tissues. h Schematic diagram for low glucose and metformin-induced cell apoptosis