Metformin enhances anti-tumor effect of L-type amino acid transporter 1 (LAT1) inhibitor

Background in many cancer cells,l-type amino acid transporter 1 (lat1) transports neutral amino acids with bulky side chain,which activate mammalian target of rapamycin (mtor) to cause cell proliferation. an anti-diabetic drug,metformin,has been shown to activate amp-activated protein kinase (ampk),which leads to inhibition of mtor. lat1 inhibition in combination with metformin could result in more prominent suppression of mtor activity. purpose anti-proliferative effect of a newly developed lat1 specific inhibitor jph203 in combination with metformin is evaluated in 2 head and neck cancer cell lines,ca9-22 and hep-2 cells and in nude mice inoculated with ca9-22 cells. results and discussion by mtt assay,0.5 mm metformin inhibited proliferation of ca9-22 cells to 70% of control. in the presence of 100 μm jph203,proliferation of ca9-22 cells was inhibited to 60% of control. by combining these 2 drugs,proliferation of ca9-22 was significantly inhibited to 40% of control. however,this regimen was not very effective against hep-2 cells. this combination also suppressed in vivo growth of ca9-22 cells in a xenotransplant model. a combination of anti-lat1 drug with metformin may be an effective anti-proliferative therapy for certain subsets of cancers. © 2016 the authors