PMID- 21270604
OWN - NLM
STAT- MEDLINE
DCOM- 20110701
LR  - 20181030
IS  - 1525-1438 (Electronic)
IS  - 1048-891X (Linking)
VI  - 21
IP  - 2
DP  - 2011 Feb
TI  - Metformin reverses progestin resistance in endometrial cancer cells by 
      downregulating GloI expression.
PG  - 213-21
LID - 10.1097/IGC.0b013e318207dac7 [doi]
AB  - INTRODUCTION: A long-term treatment with progestin commonly results in progestin 
      resistance in endometrial cancer. So, the aim of this study was to investigate 
      the role of glyoxalase I (GloI), a mediator of chemotherapy resistance, in 
      metformin reversal of progestin resistance in endometrial carcinoma. METHODS: The 
      proliferation variety of endometrial cancer cells was determined by 3-(4, 
      5-dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium (MTT) assay after exposure to 
      medroxyprogesterone acetate, metformin, or both reagents; apoptosis rates were 
      assessed by flow cytometry. Real-time polymerase chain reaction was used to 
      evaluate the effect of small interfering RNA sequence on target gene expression. 
      Western immunoblotting was performed to determine the expression of GloI and the 
      molecules of the mammalian target of rapamycin (mTOR) pathway. RESULT: Knocking 
      down GloI sensitized progestin-resistant Ishikawa cells to progestin. Metformin 
      downregulated GloI expression, reversed progestin resistance, enhanced 
      progestin-induced cell proliferation inhibition, and induced apoptosis in 
      progestin-resistant Ishikawa cells. In addition, medroxyprogesterone 
      acetate-induced mTOR phosphorylation was blocked by metformin. Metformin 
      abolishes mTOR phosphorylation and inhibits GloI expression, attenuating 
      proliferation and inducing apoptosis in progestin-resistant Ishikawa cells. 
      CONCLUSIONS: Dysregulation of GloI expression in endometrial cancer may be part 
      of the molecular mechanisms for progestin resistance.
FAU - Zhang, Zhenbo
AU  - Zhang Z
AD  - Department of Obstetrics and Gynecology, Shanghai Jiao Tong University, Shanghai, 
      China.
FAU - Dong, Lingling
AU  - Dong L
FAU - Sui, Long
AU  - Sui L
FAU - Yang, Yixia
AU  - Yang Y
FAU - Liu, Xuelian
AU  - Liu X
FAU - Yu, Yinhua
AU  - Yu Y
FAU - Zhu, Yaping
AU  - Zhu Y
FAU - Feng, Youji
AU  - Feng Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Gynecol Cancer
JT  - International journal of gynecological cancer : official journal of the 
      International Gynecological Cancer Society
JID - 9111626
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Progestins)
RN  - 9100L32L2N (Metformin)
RN  - EC 4.4.1.5 (Lactoylglutathione Lyase)
SB  - IM
CIN - Int J Gynecol Cancer. 2012 Feb;22(2):181. PMID: 22274313
MH  - Apoptosis
MH  - Carcinoma, Endometrioid/*drug therapy/metabolism
MH  - Down-Regulation
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Endometrial Neoplasms/*drug therapy/metabolism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Female
MH  - Humans
MH  - Lactoylglutathione Lyase/*metabolism
MH  - Metformin/*pharmacology
MH  - Progestins/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2011/01/29 06:00
MHDA- 2011/07/02 06:00
CRDT- 2011/01/29 06:00
PHST- 2011/01/29 06:00 [entrez]
PHST- 2011/01/29 06:00 [pubmed]
PHST- 2011/07/02 06:00 [medline]
AID - 00009577-201102000-00005 [pii]
AID - 10.1097/IGC.0b013e318207dac7 [doi]
PST - ppublish
SO  - Int J Gynecol Cancer. 2011 Feb;21(2):213-21. doi: 10.1097/IGC.0b013e318207dac7.