Back to Search
Start Over
Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression.
- Source :
-
The journal of obstetrics and gynaecology research [J Obstet Gynaecol Res] 2012 Aug; Vol. 38 (8), pp. 1077-85. Date of Electronic Publication: 2012 Apr 30. - Publication Year :
- 2012
-
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.<br />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.<br />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.<br />Conclusion: Metformin enhances the rate of cell-killing induced by chemotherapeutic agents by repressing GloI expression.<br /> (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)
- Subjects :
- Antineoplastic Agents therapeutic use
Carcinoma, Endometrioid enzymology
Cell Line, Tumor
Cell Proliferation drug effects
Cisplatin therapeutic use
Drug Evaluation, Preclinical
Drug Synergism
Endometrial Neoplasms enzymology
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Hypoglycemic Agents pharmacology
Lactoylglutathione Lyase genetics
Metformin pharmacology
Paclitaxel therapeutic use
Carcinoma, Endometrioid drug therapy
Endometrial Neoplasms drug therapy
Hypoglycemic Agents therapeutic use
Lactoylglutathione Lyase metabolism
Metformin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1447-0756
- Volume :
- 38
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The journal of obstetrics and gynaecology research
- Publication Type :
- Academic Journal
- Accession number :
- 22540333
- Full Text :
- https://doi.org/10.1111/j.1447-0756.2011.01839.x