Fig. 4
Metformin and ATO in combination potentiate the antiproliferative and pro-apoptotic effect of the single agent treatments in vivo through mTORC1, AMPK/MAPK, and ERK3 pathways. a CCLP-1 cells were implanted subcutaneously into the flank regions of nude mice. When the tumor volume reached approximately 100 mm3, vehicle (NS), metformin, ATO, or a combination of both were administered. (Combination vs metformin or combination vs ATO * P < 0.05). After 3 weeks, the mice were euthanized, and the tumors are shown. b and c Tumor volume and tumor weight were measured. d The weight of mice in each group was compared. e Representative hematoxylin-eosin (HE) stained images are shown, and the expression of Ki67 and cleaved caspase-3 in the tumors was detected by IHC. In addition, apoptotic cells in the xenografted tumors were detected by TUNEL assay. f The data were quantified and are presented as the means ± SD from three independent experiments. g The effect of metformin and ATO single or combination treatment on the active status of mTORC1, AMPK/MAPK, and ERK3 in xenografts was determined by western blotting. The data were quantified and are represented as the means ± SD. (Combination vs metformin * P < 0.05, combination vs ATO # P < 0.05)