PMID- 31841183
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20221207
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 23
DP  - 2019 Dec
TI  - Mechanism of metformin enhancing the sensitivity of human pancreatic cancer cells 
      to gem-citabine by regulating the PI3K/Akt/mTOR signaling pathway.
PG  - 10283-10289
LID - 19666 [pii]
LID - 10.26355/eurrev_201912_19666 [doi]
AB  - OBJECTIVE: To investigate the effect of metformin (MET) on enhancing the 
      sensitivity of human pancreatic cancer cells to gemcitabine (GEM) by regulating 
      the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target 
      of rapamycin (mTOR) signaling pathway. MATERIALS AND METHODS: The GEM-resistant 
      human pancreatic cancer PANC-1/GEM cell line was established, and the 
      proliferation ability of PANC-1 and PANC-1/GEM cell lines was detected using the 
      Cell Counting Kit-8 (CCK-8), which was then detected by flow cytometry after they 
      were labeled by Ki67. Quantitative Reverse Transcription-Polymerase Chain 
      Reaction (qRT-PCR) and Western blotting were adopted to detect the difference in 
      the mTOR expression between PANC-1 and PANC-1/GEM cell lines. The proliferation 
      ability of PANC-1/GEM/MET and PANC-1/GEM cell lines was determined using CCK-8 
      after drug-resistant cell lines were treated with 20 mmol/L MET combined with 0.4 
      mumol/L GEM or 0.4 mumol/L GEM alone for 48 h. Colony formation assay was applied 
      to detect the proliferation ability of cells. The difference in the expression of 
      mTOR/PI3K/Akt between PANC-1/GEM/MET and PANC-1/GEM cell lines was tested via 
      qRT-PCR and Western blotting, respectively. RESULTS: Compared with PANC-1 cells, 
      PANC-1/GEM cells had significantly enhanced proliferation ability (p<0.01). Flow 
      cytometry results showed that the proliferation ability of PANC-1/GEM cells was 
      notably enhanced (p<0.01). The expression level and phosphorylation level of mTOR 
      in drug-resistant cell lines were increased (p<0.01). After the drug-resistant 
      cell lines were treated with 20 mmol/L MET for 48 h, the proliferation ability of 
      PANC-1/GEM/MET cells was evidently decreased compared with that of PANC-1/GEM 
      cells (p<0.01). The messenger ribonucleic acid (mRNA) and protein expression 
      levels of mTOR/PI3K/Akt were markedly down-regulated (p<0.01). CONCLUSIONS: MET 
      can regulate the PI3K/Akt/mTOR signaling pathway to enhance the sensitivity of 
      human pancreatic cancer cells to GEM.
FAU - Zhou, H-Y
AU  - Zhou HY
AD  - Department of Gastroenterology, Affiliated Wujiang Hospital of Nantong 
      University, Suzhou, China. xiangyun19881015@126.com.
FAU - Yao, X-M
AU  - Yao XM
FAU - Chen, X-D
AU  - Chen XD
FAU - Tang, J-M
AU  - Tang JM
FAU - Qiao, Z-G
AU  - Qiao ZG
FAU - Wu, X-Y
AU  - Wu XY
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0W860991D6 (Deoxycytidine)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (MTOR protein, human)
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)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Deoxycytidine/*analogs & derivatives/pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Metformin/*pharmacology
MH  - Pancreatic Neoplasms/*metabolism
MH  - Phosphatidylinositol 3-Kinase/*biosynthesis
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/*biosynthesis
MH  - TOR Serine-Threonine Kinases/*biosynthesis
MH  - Tumor Stem Cell Assay
MH  - Gemcitabine
EDAT- 2019/12/17 06:00
MHDA- 2020/11/11 06:00
CRDT- 2019/12/17 06:00
PHST- 2019/12/17 06:00 [entrez]
PHST- 2019/12/17 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
AID - 19666 [pii]
AID - 10.26355/eurrev_201912_19666 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10283-10289. doi: 
      10.26355/eurrev_201912_19666.