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 observ able medium acidification. At the biochemical level, a marked effect on phosphorylated proteins upstream of Akt, along the mTOR pathway, was observed at 6 h. These chan ges followed a time-dependent pattern linked closely to the changes in the energetic pro file. Conclusion: Together, these results indicate that metformin indirectly blocks protein phos phorylation, including that of heat shock protein 27 (HSP27).
|Number of pages||9|
|Publication status||Published - Apr 1 2015|
All Science Journal Classification (ASJC) codes
- Cancer Research