Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression

Journal of Obstetrics and Gynaecology Research, 05/15/2012

Metformin enhances the rate of cell–killing induced by chemotherapeutic agents by repressing GloI expression.

Methods

  • MTT assay was performed to determine the rate of cell death after cisplatin and paclitaxel with or without metformin.
  • Western blot was carried out to analyze GloI expression.
  • SiRNA–targeting of GloI was used to knockdown GloI expression before further treatment with chemotherapeutic agents to examine the effect of GloI downregulation on chemotherapy–induced cell killing.
  • In addition, plasmid transfection was used to overexpress GloI and determine whether high GloI levels blocked metformin–enhanced cell sensitivity to chemotherapy.
  • PCR was used to analyze the efficiency of RNA interference and plasmid transfection.

Results

  • The addition of metformin enhanced the sensitivity of endometrial cells to cisplatin and paclitaxel, which was associated with reduced levels of GloI expression.
  • Moreover, low–dose chemotherapeutic drugs alone could not significantly reduce GloI expression, whereas the addition of metformin potently downregulated GloI protein levels.
  • Cisplatin and paclitaxel markedly inhibited the proliferative ability of GloI–depleted endometrial cancer cells.
  • However, the overexpression of GloI abolished the effect of metformin–enhanced cell sensitivity to chemotherapeutic drugs.

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