Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action

Byron Baron, Yufeng Wang, Shin Ichiro Maehara, Yoshihiko Maehara, Yasuhiro Kuramitsu, Kazuyuki Nakamura

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 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).

Original languageEnglish
Pages (from-to)1941-1949
Number of pages9
JournalAnticancer research
Volume35
Issue number4
Publication statusPublished - Apr 1 2015

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gemcitabine
Metformin
Pancreatic Neoplasms
Cell Line
Lactic Acid
HSP27 Heat-Shock Proteins
Proteins
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Baron, B., Wang, Y., Maehara, S. I., Maehara, Y., Kuramitsu, Y., & Nakamura, K. (2015). Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action. Anticancer research, 35(4), 1941-1949.

Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action. / Baron, Byron; Wang, Yufeng; Maehara, Shin Ichiro; Maehara, Yoshihiko; Kuramitsu, Yasuhiro; Nakamura, Kazuyuki.

In: Anticancer research, Vol. 35, No. 4, 01.04.2015, p. 1941-1949.

Research output: Contribution to journalArticle

Baron, B, Wang, Y, Maehara, SI, Maehara, Y, Kuramitsu, Y & Nakamura, K 2015, 'Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action', Anticancer research, vol. 35, no. 4, pp. 1941-1949.
Baron B, Wang Y, Maehara SI, Maehara Y, Kuramitsu Y, Nakamura K. Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action. Anticancer research. 2015 Apr 1;35(4):1941-1949.
Baron, Byron ; Wang, Yufeng ; Maehara, Shin Ichiro ; Maehara, Yoshihiko ; Kuramitsu, Yasuhiro ; Nakamura, Kazuyuki. / Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action. In: Anticancer research. 2015 ; Vol. 35, No. 4. pp. 1941-1949.
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