PMID- 33099954 OWN - NLM STAT- MEDLINE DCOM- 20210721 LR - 20211204 IS - 2241-6293 (Electronic) IS - 1107-0625 (Linking) VI - 25 IP - 4 DP - 2020 Jul-Aug TI - Metformin induces apoptosis of melanoma B16 cells via PI3K/Akt/mTOR signaling pathways. PG - 2066-2070 AB - PURPOSE: To investigate the influences of metformin on the proliferation and apoptosis of mouse melanoma B16 cells through regulating the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: The mouse melanoma B16 cell strains were taken as the subjects of the study, and were randomly divided into the control group with RPMI-640 medium with the volume same with that in the metformin group (C group, n=6) and Q group [metformin:10 mmol/L (Q1 group, n=6), metformin:20 mmol/L (Q2 group, n=6), and metformin:40 mmol/L (Q3 group, n=6)]. The cell counting kit-8 (CCK-8) method was employed to detect the proliferation of cells in each group at different culture times. The apoptosis of cells in each group was detected via flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: The proliferation rate in Q group was lower than in C group, and the difference was statistically significant (p<0.05 or p<0.01). According to the results of flow cytometry, it was concluded that the number of apoptotic cells in Q group was higher than in C group (p<0.05 or p<0.01). TUNEL results revealed that compared with that in C group, the apoptosis rate in Q group was increased (p<0.05 or p<0.01). Moreover, western blotting results showed that the protein expression levels of PI3K, Akt and mTOR in Q group were higher than in C group. CONCLUSIONS: Metformin can inhibit the proliferation of mouse melanoma B16 cells and induce their apoptosis probably through its regulation on the PI3K/AKT/mTOR signaling pathway in cells. FAU - Tian, Ye AU - Tian Y AD - Department of Dermatology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, China. FAU - Zhao, Lili AU - Zhao L LA - eng PT - Journal Article PL - Cyprus TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Cell Proliferation/drug effects MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Melanoma, Experimental/*drug therapy/metabolism/pathology MH - Metformin/*pharmacology MH - Mice MH - Phosphatidylinositol 3-Kinase/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Random Allocation MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/*metabolism EDAT- 2020/10/26 06:00 MHDA- 2021/07/22 06:00 CRDT- 2020/10/25 20:18 PHST- 2020/10/25 20:18 [entrez] PHST- 2020/10/26 06:00 [pubmed] PHST- 2021/07/22 06:00 [medline] PST - ppublish SO - J BUON. 2020 Jul-Aug;25(4):2066-2070.