1. Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression.
- Author
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Dong, Lingling, Zhou, Qian, Zhang, Zhenbo, Zhu, Yaping, Duan, Tao, and Feng, Youji
- Subjects
CANCER chemotherapy ,CHEMILUMINESCENCE assay ,COMBINATION drug therapy ,CISPLATIN ,DRUG synergism ,GENE expression ,PACLITAXEL ,POLYMERASE chain reaction ,PROGESTATIONAL hormones ,RESEARCH funding ,SPECTRUM analysis ,T-test (Statistics) ,WESTERN immunoblotting ,ENDOMETRIAL tumors ,DISEASE remission ,METFORMIN ,REVERSE transcriptase polymerase chain reaction ,DATA analysis software ,DESCRIPTIVE statistics ,PHARMACODYNAMICS - Abstract
Aim: Metformin plays an important role in the inhibition of cancer cell growth and prolongs remission durations. It reverses progestin-resistance in endometrial cancer cells by downregulating glyoxalase I (GloI) expression. This study aimed to investigate the effect of metformin on endometrial cancer cell chemotherapeutic sensitivity and explore the underlying molecular mechanisms. Material and 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. Conclusion: Metformin enhances the rate of cell-killing induced by chemotherapeutic agents by repressing GloI expression. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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