PMID- 32495867
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20211204
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 24
IP  - 10
DP  - 2020 May
TI  - Metformin reduces pancreatic cancer cell proliferation and increases apoptosis 
      through MTOR signaling pathway and its dose-effect relationship.
PG  - 5336-5344
LID - 21316 [pii]
LID - 10.26355/eurrev_202005_21316 [doi]
AB  - OBJECTIVE: To study the influences of metformin on the proliferation and 
      apoptosis of pancreatic cancer cells and its dose-effect relationship and crucial 
      molecular mechanism. MATERIALS AND METHODS: With human pancreatic cancer cell 
      line PANC-1 as the study object, different concentrations of metformin were added 
      for intervention. Then, the proliferation of PANC-1 cells was detected via methyl 
      thiazolyl tetrazolium (MTT) assay to determine the dose-effect relationship of 
      metformin in PANC-1 cell proliferation. PANC-1 cells were treated with metformin 
      at three appropriate concentrations as Metformin treatment groups, and an equal 
      amount of dimethyl sulfoxide (DMSO) was added in Control group. Flow cytometry 
      was performed to detect PANC-1 cell cycle and apoptosis, and the apoptosis of 
      PANC-1 cells was also evaluated via terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) assay. Caspase-3 protein 
      localization and expression in PANC-1 cells were detected using 
      immunofluorescence assay. Besides, the expressions of the apoptosis-associated 
      proteins Caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2 associated X protein 
      (Bax) and phosphatidylinositol 3-hydroxy kinase (PI3K), phosphorylated protein 
      kinase B (p-Akt), and p-mammalian target of rapamycin (mTOR) proteins related to 
      the mTOR pathway were detected using Western blotting. RESULTS: Metformin 
      repressed the proliferation of human pancreatic cancer PANC-1 cells in a 
      concentration-dependent and time-dependent manner. Compared with Control group, 
      Metformin treatment groups (0, 20 and 40 mM) exhibited a higher proportion of 
      PANC-1 cells in G0/G1 phases, and a lower proportion of PANC-1 cells in S phase 
      (p<0.05), and the change in the proportion of cells in G2/M phase was not 
      statistically significant (p>0.05). Moreover, Metformin treatment groups (0, 20, 
      and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of 
      pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of 
      anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, 
      and p-mTOR in cells than Control group (p<0.05). CONCLUSIONS: Metformin modulates 
      the mTOR signaling pathway to reduce the proliferation of pancreatic cancer cell, 
      but increase their apoptosis.
FAU - Zhao, H-W
AU  - Zhao HW
AD  - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, 
      China. zhaojianqizjq@163.com.
FAU - Zhou, N
AU  - Zhou N
FAU - Jin, F
AU  - Jin F
FAU - Wang, R
AU  - Wang R
FAU - Zhao, J-Q
AU  - Zhao JQ
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Antineoplastic Agents)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Metformin/*pharmacology
MH  - Pancreatic Neoplasms/*drug therapy/metabolism/pathology
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2020/06/05 06:00
MHDA- 2021/04/01 06:00
CRDT- 2020/06/05 06:00
PHST- 2020/06/05 06:00 [entrez]
PHST- 2020/06/05 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
AID - 21316 [pii]
AID - 10.26355/eurrev_202005_21316 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2020 May;24(10):5336-5344. doi: 
      10.26355/eurrev_202005_21316.