Abstract:
Objective To test the effect of different glucose levels on the anti-tumor effect of metformin and explore its mechanism.
Methods Cells cultured in the mediums with different glucose levels were treated with metformin for 24 hours. Then, we detected cell proliferation and ATP levels. A subcutaneous xenograft tumor model was established in nude mice in vivo. Nude mice were randomly divided into four groups: standard diet(SD) group, SD+metformin(Met) group, ketogenic diet(KD) group and KD+Met group. After 8 weeks of experimental intervention, tumor volume and weight and blood glucose level in nude mice were detected.
Results Metformin did not inhibit the proliferation of pancreatic cancer cells when the glucose level was above 10mmol/L, but 10mmol/L metformin significantly inhibited the proliferation of pancreatic cancer cells in low glucose medium (≤5mmol/L). At the same time, the ATP level of each cell in low glucose medium was significantly decreased (P < 0.01). In vivo, blood glucose level was significantly decreased in KD group (P < 0.01), and KD significantly inhibited tumor growth (P < 0.01). Compared with KD group, KD+Met group could further inhibit the growth of the xenografts (P < 0.05).
Conclusion Low glucose enhances the sensitivity of cancer to metformin and metformin exerts anti-tumor effect by reducing the body's ATP production.
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