Byron Baron1, Yufeng Wang2, Shin-Ichiro Maehara3, Yoshihiko Maehara3, Yasuhiro Kuramitsu2, Kazuyuki Nakamura4. 1. Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Japan Department of Anatomy and Cell Biology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta angenlabs@gmail.com. 2. Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Japan. 3. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 4. Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Japan Centre of Clinical Laboratories in Tokuyama Medical Association Hospital, Shunan-shi, Japan.
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 marked 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). Copyright
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 marked 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). Copyright
Authors: Audrius Dulskas; Ausvydas Patasius; Donata Linkeviciute-Ulinskiene; Lina Zabuliene; Giedre Smailyte Journal: Int J Environ Res Public Health Date: 2020-08-19 Impact factor: 3.390