Metformin (MET), either alone or in combination with other drugs, has been considered a promising drug in cancer therapy. MET via activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and inhibiting the mammalian target of rapamycin (mTOR) mediates tumor proliferation. Moreover, as an antagonist of the histamine H2-receptor (H2R), cimetidine (CIM) is also attributed to several immune-stimulatory responses in non-immunogenic cancers. Moreover, non-efficient inflammatory responses derived from prostaglandins may contribute to interleukin-6 (IL-6) production and tumor progression, which ibuprofen (IBU) hinders. Due to the significant effects of these drugs in the modulation of antitumor immunity and hindrance of tumor progression, it seems reasonable to assess their combinational therapy in the breast cancer (BC) mouse model.
Metformin, Cimetidine, Ibuprofen, Signal transduction, TOR serine-threonine kinases