Combined 2-deoxy glucose and metformin improves therapeutic efficacy of
sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer
cells
#MMPMID26355636
Chatterjee S
; Thaker N
; De A
Breast Cancer (Dove Med Press)
2015[]; 7
(?): 251-65
PMID26355636
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Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various
cancer cells has been reported. The present study reveals novel information on
combining these drugs to enhance radiosensitization effect in breast cancer (BC)
cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged
radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or
SLC5A5) protein, are tested. As therapeutic potential of NIS in BC is often
limited due to low uptake and fast efflux rate of iodine, the scope of these two
radiosensitizers to further improve NIS-mediated (131)I therapeutic efficacy is
explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal
drug doses required for radiosensitization. A combination of 2 mM metformin and
20 mM 2-DG with 2 grey (Gy) Cobalt60 radiation shows significant
radiosensitization effect (P=0.0002). In cells treated with the combination
therapy, increased ?H2A.X foci formation was noted. Further, MCF-7 BC cells
overexpressing NIS (MCF-7 NIS) was established, and using the optimized drug
concentrations, significant radiosensitization (P=0.0019) by 50 ? Ci (131)I usage
was found to be the case as well. Apoptosis data corroborates with the result of
clonogenic assay showing significant increase in apoptotic population upon dual
drug-mediated radiosensitization. In case of metformin treatment, lowered
adenosine triphosphate (ATP) content of the cell has been observed. The
encouraging radiosensitization effect observed using combined 2-DG and metformin
may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine
therapy in BC cells with NIS expression. This study indicates high potential of
this drug combination in sensitizing BC cells for NIS-mediated-targeted
radioiodine therapy, which otherwise may have lacked efficacy.
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