@article {BARON1941, author = {BYRON BARON and YUFENG WANG and SHIN-ICHIRO MAEHARA and YOSHIHIKO MAEHARA and YASUHIRO KURAMITSU and KAZUYUKI NAKAMURA}, title = {Resistance to Gemcitabine in the Pancreatic Cancer Cell Line KLM1-R Reversed by Metformin Action}, volume = {35}, number = {4}, pages = {1941--1949}, year = {2015}, publisher = {International Institute of Anticancer Research}, abstract = {Background/Aim. The pancreatic cancer cell line KLM1 can gain chemoresistance following gemcitabine (GEM) treatment. Metformin was found to be a useful sensitising agent towards GEM treatment following gain of chemoresistance. Materials and Methods: The proliferation of GEM-sensitive and -resistant cells was investigated over a range of metformin concentrations from 0.005 to 5 mM. The intra- and extra-cellular energetic profiles of these two cell types under metformin exposure were investigated through adenosine triphosphate (ATP) and L-lactate assays. Results: There was an unexpected decrease in intracellular L-lactate following gain of chemoresistance, despite observable medium acidification. At the biochemical level, a mar ked effect on phosphorylated proteins upstream of Akt, along the mTOR pathway, was observed at 6 h. These changes followed a time-dependent pattern linked closely to the changes in the energetic profile. Conclusion: Together, these results indicate that metformin indirectly blocks protein phosphorylation, including that of heat shock protein 27 (HSP27).}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/35/4/1941}, eprint = {https://ar.iiarjournals.org/content/35/4/1941.full.pdf}, journal = {Anticancer Research} }