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. 2016 Feb;11(2):1287-1293.
doi: 10.3892/ol.2016.4075. Epub 2016 Jan 7.

Metformin: A candidate for the treatment of gynecological tumors based on drug repositioning

Haruko Irie  1 , Kouji Banno  1 , Megumi Yanokura  1 , Miho Iida  1 , Masataka Adachi  1 , Kanako Nakamura  1 , Kiyoko Umene  1 , Yuya Nogami  1 , Kenta Masuda  1 , Yusuke Kobayashi  1 , Eiichiro Tominaga  1 , Daisuke Aoki  1
Affiliations

Metformin: A candidate for the treatment of gynecological tumors based on drug repositioning

Haruko Irie et al. Oncol Lett. 2016 Feb.

Abstract

Metformin is a first-line drug used for the treatment of type 2 diabetes. Recently, metformin has been reported to reduce the carcinogenic risk and inhibit tumor cell growth in glioma and breast cancer. The anticancer action of metformin involves the enhancement of phosphorylation of liver kinase B1, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin, which reduces cell growth. Metformin is anticipated to exert antitumor effects in gynecological cancer, and its efficacy for the treatment of endometrial, breast and ovarian cancer has been suggested in preclinical studies and clinical trials. Although the effect of metformin on cervical cancer remains to be examined in clinical trials, its antitumor effects have been reported in preclinical studies. Thus, the use of metformin for the treatment of gynecological cancer may become a successful example of drug repositioning, following establishment of the drug's antitumor effects, risk evaluation, screening and validation of efficacy.

Keywords: breast cancer; drug repositioning; endometrial cancer; metformin; ovarian cancer.

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Figures

Figure 1.
Figure 1.
Structure of metformin. Metformin contains two conjugated guanidine groups and an additional amine.
Figure 2.
Figure 2.
Antitumor mechanism of metformin. The primary pathway is considered to be the AMPK/PI3K/Akt/mTOR signal transduction pathway. Recent studies (,–32,35) have revealed that multiple signaling pathways contribute to the antitumor mechanism of metformin. AMPK, adenosine monophosphate-activated protein kinase; PI3K, phosphoinositide 3-kinase; mTOR, mammalian target of rapamycin; LKB1, liver kinase B1.
Figure 3.
Figure 3.
Antitumor effects of metformin in gynecological cancer. Antitumor effects of metformin have been demonstrated in endometrial, ovarian, breast and cervical cancer in vitro (,–48,54,61). AMPK, adenosine monophosphate-activated protein kinase; PI3K, phosphoinositide 3-kinase; mTOR, mammalian target of rapamycin; PR, progesterone receptor; MPA, medroxyprogesterone acetate; S6K, S6 kinase.
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