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.
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.
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.