Fig. 5

Metformin enhanced chemotherapy and rituximab’s activity in vitro and in vivo. a, b Metformin enhances doxorubicin and dexamethasone anti-tumor killing activity in RSCL and RRCL. RSCL and RRCL were exposed to metformin for 48 h and changes in cell viability assessed by the change in Presto blue reduction as measured by flow cytometry. Data represented mean ± SD derived from 3 independent experiments. Asterisk means P < 0.05. c Metformin enhanced anti-CD20 antibody-mediated complement-mediated cytotoxicity (CMC) and antibody-dependent cellular cytotoxicity (ADCC) in RSCL and RRCL. Cells were exposed to media or metformin for 24 h and subsequently labeled with ⁵¹Cr. Labeled cells were then exposed to isotype or anti-CD20 antibodies, and 20% human serum pooled from healthy volunteers (CMC) or peripheral blood mononuclear cells at an effector:target ratio of 40:1 (ADCC) and incubated at 37 °C, 5% CO₂ for 6 h. ⁵¹Cr release was measured and the percentage of lysis was calculated. Asterisk means P < 0.05. d Metformin potentiated the anti-tumor activity of rituximab in mouse. Survival differences between groups were compared using log-rank analysis. Experiments were repeated in three separate times. The survival difference between rituximab as a single agent compared to rituximab combined with metformin at 2 μg/ml dosage was found to be significant (P = 0.01)