PT  - JOURNAL ARTICLE
AU  - HIROKI YAMANA
AU  - KIYOHITO KATO
AU  - HIDEKI KOBARA
AU  - SHINTARO FUJIHARA
AU  - KOJI FUJITA
AU  - DAISUKE NAMIMA
AU  - NAOKI FUJITA
AU  - KIYOYUKI KOBAYASHI
AU  - HIDEKI KAMADA
AU  - ASAHIRO MORISHITA
AU  - KUNIHIKO TSUTSUI
AU  - HISAKAZU IWAMA
AU  - TSUTOMU MASAKI
TI  - Metformin Inhibits Proliferation and Tumor Growth of QGP-1 Pancreatic Neuroendocrine Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis
AID  - 10.21873/anticanres.13933
DP  - 2020 Jan 01
TA  - Anticancer Research
PG  - 121--132
VI  - 40
IP  - 1
4099  - http://ar.iiarjournals.org/content/40/1/121.short
4100  - http://ar.iiarjournals.org/content/40/1/121.full
SO  - Anticancer Res2020 Jan 01; 40
AB  - Background/Aim: Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms, and therapeutic options for pNETs are limited. Metformin is an anti-hypoglycemic drug that appears to have anticancer effects. However, little is known about the effect of metformin on pNETs. In this study, we investigated the anti-proliferative effect of metformin on a human pNET cell line. Materials and Methods: The anti-proliferative properties of metformin were evaluated in QGP-1 and NCI-H727 cells using a cell counting kit-8 assay. Xenograft mouse models were used to assess the tumor effect in vivo. Results: Metformin inhibited the proliferation and anti-tumor growth of QGP-1 cells, accompanied by their arrest during the cell cycle at the G0/G1 phase. Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group. Additionally, metformin induced apoptosis, and the expression of survivin and claspin were decreased in metformin-treated QGP-1 cells according to the apoptosis array. Furthermore, the angiogenic related protein TIMP-1 was down-regulated, and its miRNA expression was altered by metformin in QGP-1 cells. Conclusion: Taken together, our study demonstrated the therapeutic potential of metformin and provides molecular mechanistic insights into its anti-tumoral effect on pNETs. This study is the first one describing anti-tumoral effects in pNETs.