Metformin Liposome Specifically Enhanced Glucose Uptake of TAMs for the Alteration of Glucose Distribution in B16-TAMs Co-Culture System

This study investigated the possibility that Met-lipo (metformin liposome) altered glucose distribution within B16-TAMs co-culture system and inhibited the growth of B16 cells by specifically enhancing glucose uptake of TAMs (tumor-associated macrophages). 2-NBDG was used as glucose analogue to simulate glucose uptake of cells. The effect of Met (metformin) on glucose uptake of TAMs was detected by 2-NBDG uptake assay and glucose/lactate kits. The ability of Met-treated TAMs to alter glucose distribution within B16-TAMs co-culture system was also evaluated. Wound healing assay, cell proliferation assay and q-PCR were used to assess the ability of Met-treated TAMs to inhibit the proliferation and migration of B16 cells. Meanwhile, Met-lipo was prepared by ammonium sulfate gradient method and particle size, zeta potential, stability and drug-loading efficiency of liposome were detected by DLS and HPLC. Furthermore, the antitumor effect and ability of Met-lipo to alter glucose distribution within B16-TAMs contact co-culture system was also evaluated by 2-NBDG uptake assay, wound healing assay, cell proliferation assay and q-PCR analysis. Results showed that the treatment of Met (10 mmol/L) could effectively enhance the glucose uptake efficiency of TAMs, which could deprive the glucose B16 cells needed. Notably, the prepared Met-lipo could specifically enhance the glucose uptake of TAMs in B16-TAMs co-culture system and exhibited more prominent antitumor effect than free Met. In conclusion, Met-lipo could specifically enhance glucose uptake of TAMs and alter the glucose distribution within B16-TAMs co-culture system, and then inhibit the proliferation and migration of B16 cells.

CSTR: 32200.14.cjcb.2022.05.0007